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Trial record 73 of 101 for:    Risedronate

A Phase II/III, Double-blind, Parallel Group Comparative Study of Oral Administration of NE-58095 Tablets

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02063854
Recruitment Status : Completed
First Posted : February 14, 2014
Results First Posted : February 23, 2017
Last Update Posted : February 23, 2017
Sponsor:
Collaborator:
EA Pharma Co., Ltd.
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Involutional Osteoporosis
Interventions Drug: NE-58095 IR
Drug: NE-58095 IR Placebo
Drug: NE-58095 DR
Drug: NE-58095 DR Placebo
Enrollment 871
Recruitment Details Participants took part in the study at 67 investigative sites in Japan from 21 February 2014 to 19 November 2015.
Pre-assignment Details Participants with a diagnosis of involutional osteoporosis were randomized at a ratio of 3:1:3:1:1:3:1 into 1 of 7 treatment groups: once-daily NE-58095 2.5 mg immediate release (IR) or once-monthly NE-58095 25 mg or 37.5 mg delayed release (DR) on awakening, after breakfast or 30 minutes following breakfast.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Period Title: Overall Study
Started 199 66 206 68 65 201 66
Full Analysis Set: Received Study Drug 199 66 206 68 65 200 66
Completed 178 54 176 58 54 170 60
Not Completed 21 12 30 10 11 31 6
Reason Not Completed
Pretreatment Event/Adverse Event             13             10             13             8             7             18             4
Major Protocol Deviation             0             0             3             0             0             0             0
Voluntary Withdrawal             2             0             8             1             3             6             1
Surgical Dental Work Performed/Planned             5             2             6             1             1             6             1
Reason Not Specified             1             0             0             0             0             0             0
Did Not Receive Study Drug             0             0             0             0             0             1             0
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast Total
Hide Arm/Group Description NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. Total of all reporting groups
Overall Number of Baseline Participants 199 66 206 68 65 201 66 871
Hide Baseline Analysis Population Description
Randomized set included all participants who were randomized to the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
68.9  (7.32) 69.0  (8.18) 68.2  (7.68) 68.4  (7.24) 69.0  (6.98) 69.6  (7.19) 69.8  (7.87) 68.9  (7.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Female
190
  95.5%
64
  97.0%
203
  98.5%
66
  97.1%
63
  96.9%
198
  98.5%
63
  95.5%
847
  97.2%
Male
9
   4.5%
2
   3.0%
3
   1.5%
2
   2.9%
2
   3.1%
3
   1.5%
3
   4.5%
24
   2.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
199 66 206 68 65 201 66 871
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
152.1  (6.59) 151.0  (6.64) 151.9  (6.11) 152.5  (5.49) 153.5  (5.13) 151.3  (5.20) 151.9  (6.47) 151.9  (6.00)
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
50.52  (7.975) 49.98  (6.720) 50.20  (7.231) 50.97  (8.736) 51.26  (7.473) 50.36  (7.383) 50.51  (7.427) 50.46  (7.544)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
21.82  (3.009) 21.93  (2.830) 21.75  (2.926) 21.97  (3.875) 21.79  (3.289) 22.00  (3.105) 21.90  (3.071) 21.87  (3.092)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Smoking Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Never smoked 167 55 178 53 54 168 58 733
Current smoker 10 4 11 3 3 7 3 41
Ex-smoker 22 7 17 12 8 26 5 97
Menopausal Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Natural Menopause 170 58 179 60 53 180 59 759
Artificial Menopause 20 6 24 6 10 18 4 88
[1]
Measure Description: Female participants only (N=190, 64, 203, 66, 63, 198, 63).
Number of Years After Menopause, Categorical   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Min - ≤5 years 6 5 7 4 3 4 2 31
6 - ≤10 years 23 1 28 4 8 22 6 92
11 - ≤20 years 59 21 71 29 20 61 20 281
21 - ≤30 years 55 19 42 12 19 58 19 224
≥31 years 9 6 11 7 4 17 4 58
Unknown, But >2 years 38 12 44 10 9 36 12 161
[1]
Measure Description: Female participants only (N=190, 64, 203, 66, 63, 198, 63).
Number of Years After Menopause   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
18.6  (7.81) 20.2  (8.72) 17.2  (8.44) 18.3  (8.28) 19.2  (8.36) 19.5  (8.41) 20.1  (7.84) 18.7  (8.28)
[1]
Measure Description: Data was available for 152, 52, 159, 56, 54, 162 and 51 female participants in each treatment arm, respectively.
History of Bisphosphonate Administration  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Yes 19 6 24 8 9 26 6 98
No 180 60 182 60 56 175 60 773
Timing of Initial Delayed Release (DR) Tablet Administration on Awakening   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Less than 30 Minutes before Breakfast 0 0 0 0 0 1 0 1
0.5 to 1.5 Hours before Breakfast 165 56 167 52 53 164 50 707
1.5 to 2.5 Hours before Breakfast 29 8 35 13 8 27 15 135
2.5 to 4 Hours before Breakfast 5 2 4 3 4 8 1 27
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Lumbar Spine (L2-L4) Bone Mineral Density (BMD), Categorical   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Min - ≤0.707 g/cm^2 167 46 176 54 52 158 49 702
0.708 (70%YAM) - ≤0.808 g/cm^2 24 13 21 11 10 28 11 118
0.809 (80%YAM) g/cm^2 - ≤Max 8 7 9 3 3 14 6 50
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively. YAM=young adult mean (20 to 44 years age range).
L2-L4 (BMD)   [1] 
Mean (Standard Deviation)
Unit of measure:  G/cm^2
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
0.6553  (0.09060) 0.6690  (0.11746) 0.6477  (0.08037) 0.6633  (0.08766) 0.6448  (0.08909) 0.6589  (0.09893) 0.6714  (0.09999) 0.6564  (0.09303)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
L2-L4 BMD T-score, Categorical   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Min - ≤-2.500 169 47 177 54 53 160 51 711
-2.499 - ≤-1.000 28 16 26 12 12 36 12 142
-0.999 - ≤Max 2 3 3 2 0 4 3 17
[1]
Measure Description:

BMD T-score is a comparison of an individual's BMD compared to "normal". Also, BMD T-score is the standard deviation of the difference between measured BMD and that of the healthy young adult "normal". The T-score scale is as follows: -1 and above=normal, -1 to -2.5=osteopenia (below normal and may lead to osteoporosis), and -2.5 and below=osteoporosis.

Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.

L2-L4 BMD T-score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
-2.9889  (0.76130) -2.8738  (0.98709) -3.0532  (0.67537) -2.9219  (0.73670) -3.0773  (0.74863) -2.9587  (0.83135) -2.8536  (0.84030) -2.9796  (0.78178)
[1]
Measure Description: BMD T-score is a comparison of an individual's BMD compared to "normal". Also, BMD T-score is the standard deviation of the difference between measured BMD and that of the healthy young adult "normal". The T-score scale is as follows: -1 and above=normal, -1 to -2.5=osteopenia (below normal and may lead to osteoporosis), and -2.5 and below=osteoporosis. Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Total Proximal Femur BMD   [1] 
Mean (Standard Deviation)
Unit of measure:  G/cm^2
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
0.6553  (0.08997) 0.6573  (0.09537) 0.6452  (0.08490) 0.6580  (0.07982) 0.6486  (0.06973) 0.6652  (0.08465) 0.6520  (0.07289) 0.6548  (0.08464)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Total Proximal Femur BMD T-score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
-2.1972  (0.89971) -2.1770  (0.95369) -2.2982  (0.84903) -2.1699  (0.79822) -2.2642  (0.69731) -2.0978  (0.84652) -2.2305  (0.72892) -2.2021  (0.84645)
[1]
Measure Description: BMD T-score is a comparison of an individual's BMD compared to "normal". Also, BMD T-score is the standard deviation of the difference between measured BMD and that of the healthy young adult "normal". The T-score scale is as follows: -1 and above=normal, -1 to -2.5=osteopenia (below normal and may lead to osteoporosis), and -2.5 and below=osteoporosis. Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Trochanter BMD   [1] 
Mean (Standard Deviation)
Unit of measure:  G/cm^2
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
0.4938  (0.07793) 0.4954  (0.06803) 0.4844  (0.06610) 0.4932  (0.07164) 0.4879  (0.05653) 0.5009  (0.06626) 0.4900  (0.06824) 0.4925  (0.06914)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Femoral Neck BMD   [1] 
Mean (Standard Deviation)
Unit of measure:  G/cm^2
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
0.5318  (0.07695) 0.5258  (0.08147) 0.5278  (0.07960) 0.5348  (0.07154) 0.5245  (0.06293) 0.5411  (0.08051) 0.5373  (0.07346) 0.5327  (0.07712)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Femoral Neck BMD T-score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
-2.8683  (0.85505) -2.9358  (0.90523) -2.9135  (0.88448) -2.8360  (0.79487) -2.9501  (0.69920) -2.7652  (0.89454) -2.8077  (0.81618) -2.8594  (0.85690)
[1]
Measure Description: BMD T-score is a comparison of an individual's BMD compared to "normal". Also, BMD T-score is the standard deviation of the difference between measured BMD and that of the healthy young adult "normal". The T-score scale is as follows: -1 and above=normal, -1 to -2.5=osteopenia (below normal and may lead to osteoporosis), and -2.5 and below=osteoporosis. Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Dual-Energy X-Ray Absorptiometry (DXA) Measuring Apparatus  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
QDR-4500 14 5 14 5 6 12 6 62
Delphi 28 9 29 9 9 26 8 118
Discovery 114 38 120 39 35 118 35 499
Explorer 43 14 43 15 15 45 17 192
Number of Existing Vertebral (Thoracic [Th4] -L4) Fractures   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
0 138 32 125 42 38 121 35 531
1 39 21 61 17 18 58 25 239
2 12 8 12 7 6 15 6 66
≥3 10 5 8 2 3 6 0 34
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Fragility Fracture  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Yes 86 37 91 32 31 104 36 417
No 113 29 115 36 34 97 30 454
Primary Osteoporosis Diagnosis Criteria 2012   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Fragility Fracture (Vertebrae or Proximal Femur) 65 30 82 29 25 80 32 343
Fragility Fracture (Other and BMD<YAM*80%) 21 7 9 3 6 24 4 74
No Fragility Fracture and BMD<=YAM*70% 113 29 115 35 34 97 30 453
[1]
Measure Description: Data was available for 199, 66, 206, 67, 65, 201 and 66 participants in each treatment arm, respectively. YAM=young adult mean (lumbar spine: 20 to 44 years age range, proximal femur: 20 to 29 years age range).
Serum 25-hydroxy Vitamin D (25-OH-D), Categorical   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
Min - ≤14.9 ng/mL 18 8 21 5 8 21 8 89
15.0 - ≤27.9 ng/mL 161 51 157 53 50 160 53 685
28.0 ng/mL - ≤Max 20 7 28 10 7 19 5 96
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Serum 25-OH-D   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
21.55  (5.266) 21.44  (5.423) 21.46  (5.592) 21.64  (5.427) 21.17  (5.248) 21.52  (5.121) 20.58  (4.761) 21.42  (5.288)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Serum C-telopeptide of Type 1 Collagen (CTX)   [1] 
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
0.444  (0.1660) 0.460  (0.1855) 0.426  (0.1776) 0.421  (0.1437) 0.497  (0.1867) 0.417  (0.1592) 0.399  (0.1613) 0.434  (0.1696)
[1]
Measure Description: Data was available for 199, 66, 205, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Serum Bone-type Alkaline Phosphatase (BAP)   [1] 
Mean (Standard Deviation)
Unit of measure:  μg/L
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
15.91  (5.809) 16.88  (8.617) 15.83  (6.035) 15.45  (5.024) 17.17  (7.354) 15.13  (5.164) 15.13  (6.815) 15.79  (6.142)
[1]
Measure Description: Data was available for 199, 66, 205, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Serum Tartrate-resistant Acid Phosphatase 5b (TRACP-5b)   [1] 
Mean (Standard Deviation)
Unit of measure:  mU/dL
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
427.1  (154.67) 424.1  (144.89) 422.1  (162.07) 398.4  (127.54) 444.7  (142.90) 410.5  (142.09) 395.0  (128.38) 418.5  (148.29)
[1]
Measure Description: Data was available for 199, 66, 205, 68, 65, 200 and 66 participants in each treatment arm, respectively.
Serum Procollagen 1 N-terminal Peptide (P1NP)   [1] 
Mean (Standard Deviation)
Unit of measure:  μg/L
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
51.79  (20.357) 54.91  (27.552) 50.89  (22.635) 47.83  (17.120) 53.43  (22.783) 48.53  (20.366) 46.04  (21.714) 50.44  (21.648)
[1]
Measure Description: Data was available for 198, 66, 206, 68, 64, 200 and 66 participants in each treatment arm, respectively.
Urine Type 1 Collagen Cross-linked N-telopeptide (NTX)   [1] 
Mean (Standard Deviation)
Unit of measure:  Nmol BCE/mmol-CRE
Number Analyzed 199 participants 66 participants 206 participants 68 participants 65 participants 201 participants 66 participants 871 participants
56.76  (26.169) 61.04  (34.808) 54.98  (23.928) 53.77  (22.739) 64.44  (29.535) 54.48  (23.988) 53.66  (23.911) 56.24  (25.871)
[1]
Measure Description: Data was available for 199, 66, 206, 68, 65, 200 and 66 participants in each treatment arm, respectively.
1.Primary Outcome
Title Percent Change From Baseline in Mean Lumbar Spine (L2-L4) Bone Mineral Density (BMD) Measured by Dual Energy X-Ray Absorptiometry (DXA) at End of Study
Hide Description The change in BMD in the second to the fourth lumbar vertebrae, L2 to L4, and the averages of L2 to L4 at end of study relative to baseline. DXA is a means of measuring BMD through x-ray.
Time Frame Baseline and End of Study (up to Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS), all randomized participants who received at least 1 dose of study drug, with data available for analyses.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly Following Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 190 194 181
Mean (Standard Deviation)
Unit of Measure: percent change
5.07  (4.749) 3.36  (4.332) 4.11  (4.654)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NE-58095 IR 2.5 mg Once Daily on Awakening, NE-58095 DR 37.5 mg Once Monthly Following Breakfast
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was tested using t-test at a one-sided significance level of 2.5% and a non-inferiority margin (Δ) of 1.5%.
Statistical Test of Hypothesis P-Value 0.1346
Comments [Not Specified]
Method t-test, 1 sided
Comments With a non-inferiority margin (Δ) of 1.5%.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection NE-58095 IR 2.5 mg Once Daily on Awakening, NE-58095 DR 25 mg Once Monthly Following Breakfast
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was tested using t-test at a one-sided significance level of 2.5% and a non-inferiority margin (Δ) of 1.5%.
Statistical Test of Hypothesis P-Value 0.6711
Comments [Not Specified]
Method t-test, 1 sided
Comments With a non-inferiority margin (Δ) of 1.5%.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection NE-58095 IR 2.5 mg Once Daily on Awakening, NE-58095 DR 37.5 mg Once Monthly Following Breakfast
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.96
Confidence Interval (2-Sided) 95%
-1.920 to 0.001
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection NE-58095 IR 2.5 mg Once Daily on Awakening, NE-58095 DR 25 mg Once Monthly Following Breakfast
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.71
Confidence Interval (2-Sided) 95%
-2.617 to -0.794
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection NE-58095 DR 25 mg Once Monthly Following Breakfast, NE-58095 DR 37.5 mg Once Monthly Following Breakfast
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
-0.166 to 1.658
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in Mean Lumbar Spine (L2-L4) BMD Measured by DXA at Each Visit
Hide Description The change in BMD in each vertebra, L2 to L4, and the averages of L2 to L4 at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.
Time Frame Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 6 (n=190, 62, 194, 61, 59, 181, 63) 3.18  (4.211) 1.73  (3.635) 1.92  (4.124) 2.40  (3.408) 3.67  (4.841) 2.70  (4.117) 2.64  (4.907)
Month 12 (n=178, 58, 180, 58, 55, 171, 60) 5.00  (4.783) 3.83  (4.227) 3.53  (4.423) 3.98  (3.784) 5.04  (4.387) 4.05  (4.518) 4.38  (5.277)
End of Study (n=190, 62, 194, 61, 59, 181, 63) 5.07  (4.749) 3.82  (4.158) 3.36  (4.332) 3.93  (3.714) 4.81  (4.383) 4.11  (4.654) 4.36  (5.150)
3.Secondary Outcome
Title Percent Change From Baseline in Femur (Total Proximal Femur) BMD Measured by DXA at Each Visit
Hide Description The change in BMD in the total proximal femur (whole bone, trochanteric region, and neck region) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.
Time Frame Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 6 (n=189, 62, 194, 61, 59, 180, 63) 1.10  (2.782) 0.91  (2.665) 0.43  (2.666) 0.54  (2.404) 0.77  (2.401) 0.78  (2.420) 0.55  (2.390)
Month 12 (n=181, 58, 180, 59, 55, 172, 61) 2.01  (3.316) 1.32  (3.399) 0.95  (3.233) 1.15  (3.182) 1.38  (3.013) 1.45  (2.580) 1.48  (2.880)
End of Study (n=189, 62, 194, 61, 59, 180, 63) 1.96  (3.288) 1.30  (3.309) 0.89  (3.172) 1.15  (3.131) 1.33  (2.948) 1.45  (2.565) 1.39  (2.873)
4.Secondary Outcome
Title Percent Change From Baseline in Femur (Trochanter) BMD Measured by DXA at Each Visit
Hide Description The change in BMD in the femur (trochanter) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.
Time Frame Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 6 (n=189, 62, 194, 61, 59, 180, 63) 1.34  (4.854) 1.57  (3.832) 0.70  (4.324) 0.80  (3.500) 1.46  (3.495) 1.09  (3.141) 0.53  (4.432)
Month 12 (n=181, 58, 180, 59, 55, 172, 61) 2.59  (6.007) 1.80  (4.030) 1.36  (4.632) 1.66  (4.095) 2.47  (4.129) 1.94  (3.722) 1.90  (4.259)
End of Study (n=189, 62, 194, 61, 59, 180, 63) 2.52  (5.938) 1.67  (3.951) 1.35  (4.551) 1.64  (4.038) 2.42  (4.005) 1.94  (3.661) 1.85  (4.203)
5.Secondary Outcome
Title Percent Change From Baseline in Femur (Femoral Neck) BMD Measured by DXA at Each Visit
Hide Description The change in BMD in the femur (femoral neck) at each visit relative to baseline. DXA is a means of measuring BMD through x-ray.
Time Frame Baseline and Month 6, Month 12, and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 6 (n=189, 62, 194, 61, 59, 180, 63) 1.07  (3.406) 0.90  (3.903) 0.71  (4.205) 0.49  (3.804) 1.01  (3.732) 0.57  (3.572) 0.67  (2.770)
Month 12 (n=181, 58, 180, 59, 55, 172, 61) 2.00  (4.010) 0.78  (4.302) 1.34  (4.687) 1.47  (4.055) 1.00  (3.799) 1.24  (3.492) 0.56  (4.020)
End of Study (n=189, 62, 194, 61, 59, 180, 63) 1.96  (4.017) 0.99  (4.451) 1.30  (4.638) 1.55  (4.009) 0.96  (3.754) 1.29  (3.578) 0.52  (3.962)
6.Secondary Outcome
Title Percent Change From Baseline in Bone Turnover Marker Serum Creatinine (CTX) at Each Visit
Hide Description Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study.
Time Frame Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 1 (n=199, 66, 204, 68, 65, 200, 66) -41.02  (27.396) -17.42  (27.978) -15.53  (26.107) -18.80  (25.956) -33.52  (24.667) -24.74  (28.675) -19.34  (28.442)
Month 3 (n=193, 63, 193, 65, 60, 184, 63) -47.79  (25.044) -29.29  (22.794) -24.80  (31.118) -28.76  (28.409) -36.36  (23.925) -31.30  (28.196) -29.94  (26.889)
Month 6 (n=188, 61, 190, 60, 58, 178, 63) -52.42  (22.926) -36.97  (29.126) -24.39  (38.994) -35.33  (24.539) -44.28  (24.390) -37.65  (28.327) -35.13  (25.910)
Month 9 (n=185, 60, 185, 59, 55, 175, 61) -52.44  (26.256) -33.61  (27.438) -16.75  (83.047) -27.99  (32.106) -42.94  (24.912) -34.50  (33.805) -30.97  (32.819)
Month 12 (n=181, 55, 178, 59, 54, 170, 60) -48.98  (28.051) -32.11  (32.662) -16.42  (64.139) -23.68  (44.492) -40.00  (26.613) -31.56  (36.239) -24.62  (37.156)
End of Study (n=199, 66, 204, 68, 65, 200, 66) -47.61  (28.275) -29.94  (36.896) -16.27  (60.895) -24.33  (43.256) -39.58  (26.203) -32.33  (35.959) -26.28  (36.284)
7.Secondary Outcome
Title Percent Change From Baseline in Bone Turnover Marker Serum Bone-type Alkaline Phosphatase (BAP) at Each Visit
Hide Description Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study.
Time Frame Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 1 (n=199, 66, 205, 68, 65, 200, 66) -3.04  (11.881) -2.93  (13.365) -2.61  (11.351) -3.61  (12.135) -4.16  (13.493) -3.69  (13.142) -2.44  (10.662)
Month 3 (n=193, 63, 193, 65, 60, 184, 63) -21.56  (15.047) -13.64  (18.499) -13.31  (17.846) -15.99  (19.091) -24.85  (14.835) -17.52  (18.589) -13.83  (24.858)
Month 6 (n=188, 61, 190, 60, 58, 178, 63) -28.66  (19.087) -20.92  (23.433) -17.93  (21.202) -23.90  (18.990) -31.06  (14.859) -24.06  (19.744) -23.80  (18.352)
Month 9 (n=185, 61, 185, 59, 55, 175, 61) -32.84  (17.700) -25.23  (24.949) -22.48  (22.233) -28.00  (20.334) -33.15  (16.226) -28.70  (19.536) -25.84  (21.043)
Month 12 (n=181, 55, 178, 59, 54, 170, 60) -34.53  (20.506) -29.23  (22.721) -24.91  (21.537) -30.51  (17.290) -38.06  (15.153) -29.58  (21.560) -27.74  (21.032)
End of Study (n=199, 66, 205, 68, 65, 200, 66) -33.34  (21.428) -26.27  (24.287) -23.11  (21.553) -27.21  (19.932) -33.94  (18.140) -27.52  (21.962) -27.08  (21.632)
8.Secondary Outcome
Title Percent Change From Baseline in Bone Turnover Marker Serum Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) at Each Visit
Hide Description Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study.
Time Frame Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 1 (n=199, 66, 205, 68, 65, 200, 66) -32.38  (17.664) -17.26  (20.728) -17.49  (19.406) -21.05  (17.749) -30.75  (19.626) -25.20  (19.726) -22.06  (20.097)
Month 3 (n=193, 63, 193, 65, 60, 184, 63) -37.27  (17.105) -25.46  (18.567) -23.85  (22.714) -27.46  (19.454) -33.70  (20.735) -28.36  (20.299) -27.13  (22.146)
Month 6 (n=188, 61, 190, 60, 58, 178, 63) -39.48  (17.702) -29.15  (21.223) -23.87  (27.077) -29.38  (20.340) -37.16  (18.794) -31.49  (21.748) -30.67  (21.385)
Month 9 (n=185, 61, 185, 59, 55, 175, 61) -37.64  (19.734) -25.82  (24.762) -19.44  (45.595) -24.78  (22.657) -32.78  (21.561) -28.83  (24.971) -29.71  (23.200)
Month 12 (n=181, 55, 178, 59, 54, 170, 60) -34.91  (20.628) -23.70  (25.425) -13.25  (63.783) -20.54  (26.613) -31.03  (22.287) -24.31  (26.832) -23.21  (25.372)
End of Study (n=199, 66, 205, 68, 65, 200, 66) -34.76  (20.602) -22.93  (26.532) -13.86  (60.015) -21.29  (26.141) -31.97  (21.945) -25.93  (26.283) -24.46  (25.027)
9.Secondary Outcome
Title Percent Change From Baseline in Bone Turnover Marker Serum Procollagen 1 N-terminal Peptide (P1NP) at Each Visit
Hide Description Blood samples for serum bone turnover markers were collected at specified visits according to the study schedule. Blood samples were to be collected at about the same time of the day, as far as possible, throughout the study.
Time Frame Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 1 (n=196, 66, 206, 68, 64, 200, 66) -6.55  (17.134) -9.08  (16.765) -7.70  (15.206) -9.73  (16.472) -13.68  (16.892) -9.86  (14.908) -10.07  (15.969)
Month 3 (n=192, 63, 194, 64, 59, 184, 63) -45.59  (19.379) -32.19  (27.464) -29.09  (26.955) -34.30  (20.730) -45.91  (22.176) -36.80  (29.014) -34.14  (24.153)
Month 6 (n=187, 61, 191, 60, 57, 178, 63) -50.83  (22.450) -39.51  (27.766) -33.02  (35.354) -39.21  (23.522) -51.40  (18.641) -42.21  (26.918) -40.90  (26.225)
Month 9 (n=184, 61, 186, 59, 54, 175, 61) -46.82  (29.820) -34.80  (29.523) -27.74  (38.273) -36.41  (24.862) -46.14  (21.531) -38.32  (30.139) -32.09  (36.574)
Month 12 (n=180, 55, 179, 59, 53, 170, 60) -42.90  (31.614) -35.65  (27.158) -25.32  (36.833) -31.80  (28.472) -42.75  (24.603) -31.33  (33.403) -29.11  (35.904)
End of Study (n=198, 66, 206, 68, 64, 200, 66) -41.93  (31.952) -32.03  (31.584) -25.51  (35.324) -30.67  (27.441) -40.82  (24.646) -31.74  (31.892) -29.13  (34.616)
10.Secondary Outcome
Title Percent Change From Baseline in Bone Turnover Marker Urine Type 1 Collagen Cross-linked N-telopeptide (NTX) at Each Visit
Hide Description Urine samples for urine bone turnover markers were collected at specified visits according to the study schedule. Urine samples were to be collected at about the same time of the day, as far as possible, throughout the study. Urine NTX was corrected by creatinine value.
Time Frame Baseline and Months 1, 3, 6, 9 and 12 and End of Study (Last observation carried forward at Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses. "n" in the category is the number of participants with data available at the given time-point.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 199 66 206 68 65 200 66
Mean (Standard Deviation)
Unit of Measure: percent change
Month 1 (n=199, 66, 206, 68, 65, 200, 66) -32.73  (29.296) -11.79  (38.228) -12.42  (35.178) -17.15  (40.458) -29.81  (29.087) -16.42  (39.131) -12.64  (42.198)
Month 3 (n=193, 63, 194, 65, 60, 184, 63) -37.94  (30.360) -22.32  (35.861) -15.64  (39.676) -20.24  (37.412) -31.27  (28.984) -22.60  (35.284) -20.70  (37.137)
Month 6 (n=188, 61, 191, 60, 58, 178, 63) -35.00  (35.405) -29.69  (37.178) -7.96  (52.202) -19.51  (41.804) -36.99  (28.317) -20.79  (40.913) -20.92  (38.419)
Month 9 (n=185, 61, 186, 59, 55, 175, 61) -30.97  (38.541) -17.23  (38.383) -7.71  (50.697) -19.48  (36.149) -31.25  (26.172) -15.90  (47.103) -14.07  (46.266)
Month 12 (n=181, 55, 179, 59, 54, 170, 60) -35.64  (37.715) -27.45  (33.172) -4.66  (61.863) -24.87  (34.422) -31.74  (34.664) -17.68  (55.937) -21.94  (42.649)
End of Study (n=199, 66, 206, 68, 65, 200, 66) -35.30  (37.274) -25.83  (32.786) -4.72  (59.237) -23.18  (35.863) -31.55  (35.083) -21.06  (53.671) -24.14  (42.102)
11.Secondary Outcome
Title Percentage of Participants With New Non-traumatic Vertebral Fractures (Including the Worsening of Pre-existing Fractures)
Hide Description New non-traumatic vertebral fractures were identified by interpretable X-ray images of 13 vertebrae from the fourth thoracic to the fourth lumbar vertebra. A Central Review Committee member for X-ray determined the presence or absence of new vertebral fractures, the number of new fractures, the presence or absence of worsening pre-existing vertebral fractures, and the number of worsened fractures. The assessment of new vertebral fractures and the worsening of pre-existing vertebral fractures was semiquantitative. The X-ray images were visually inspected and classified into normal (Grade 0), mild deformation (Grade 1), moderate deformation (Grade 2), or severe deformation (Grade 3). If the assessment of any vertebra became worse by at least 1 grade after starting the treatment, its height was measured. A new vertebral fracture or a worsening pre-existing vertebral fracture was concluded if the vertebra’s height was reduced from the baseline by at least 20% and by at least 4 mm.
Time Frame Baseline to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, all randomized participants who received at least 1 dose of study drug, with data available for analyses.
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description:
NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
Overall Number of Participants Analyzed 190 61 193 62 59 178 63
Measure Type: Number
Unit of Measure: percentage of participants
Yes 2.1 3.3 2.1 3.2 3.4 1.1 1.6
No 97.9 96.7 97.9 96.8 96.6 98.9 98.4
Time Frame First dose of study drug to 30 days past last dose of study drug (Up to 13 Months)
Adverse Event Reporting Description At each visit the investigator documented any occurrence of AEs and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of relation to study treatment. AEs were monitored until the participant recovered or investigator judged no further follow-up was needed.
 
Arm/Group Title NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Hide Arm/Group Description NE-58095 immediate release (IR) 2.5 mg tablet, orally, once, daily, at time of wakening + NE-58095 delayed release (DR) placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 25 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, at time of wakening + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication. NE-58095 DR 37.5 mg tablet, orally, once, monthly, 30 minutes after breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, following breakfast + NE-58095 DR placebo-matching tablet, orally, once, monthly, at time of wakening + NE-58095 IR placebo-matching tablet, orally, once, daily, at time of wakening, for up to 12 months. Calcium lactate hydrate 195 mg, once, daily, after dinner was taken as a background medication.
All-Cause Mortality
NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/199 (6.03%)   5/66 (7.58%)   11/206 (5.34%)   7/68 (10.29%)   2/65 (3.08%)   8/200 (4.00%)   3/66 (4.55%) 
Cardiac disorders               
Cardiac failure congestive  1  0/199 (0.00%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Angina pectoris  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Ear and labyrinth disorders               
Meniere's disease  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  1/65 (1.54%)  0/200 (0.00%)  0/66 (0.00%) 
Sudden hearing loss  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Vertigo  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  1/65 (1.54%)  0/200 (0.00%)  0/66 (0.00%) 
Endocrine disorders               
Goitre  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Eye disorders               
Cataract  1  2/199 (1.01%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Dacryostenosis acquired  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Gastrointestinal disorders               
Large intestine polyp  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Gastric ulcer haemorrhage  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Inguinal hernia  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
General disorders               
Drowning  1 [1]  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Hepatobiliary disorders               
Cholelithiasis  1  1/199 (0.50%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Immune system disorders               
Sarcoidosis  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Infections and infestations               
Appendicitis  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Mycobacterial infection  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Pneumonia bacterial  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Pneumonia mycoplasmal  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Injury, poisoning and procedural complications               
Fall  1  3/199 (1.51%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  2/200 (1.00%)  0/66 (0.00%) 
Humerus fracture  1  1/199 (0.50%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  1/66 (1.52%) 
Spinal compression fracture  1  1/199 (0.50%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  1/66 (1.52%) 
Accident  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  1/66 (1.52%) 
Contusion  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Facial bones fracture  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Forearm fracture  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Muscle contusion  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Procedural pain  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Radius fracture  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Road traffic accident  1  0/199 (0.00%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Metabolism and nutrition disorders               
Hyperammonaemia  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Musculoskeletal and connective tissue disorders               
Osteoarthritis  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Colon cancer metastatic  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Adenocarcinoma of colon  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Breast cancer  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Gastric cancer stage I  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Invasive ductal breast carcinoma  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Lymphoma  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  1/200 (0.50%)  0/66 (0.00%) 
Malignant neoplasm of renal pelvis  1  0/199 (0.00%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Soft tissue neoplasm  1  0/199 (0.00%)  0/66 (0.00%)  1/206 (0.49%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Uterine cancer  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Nervous system disorders               
Brain stem infarction  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  1/66 (1.52%) 
Carotid artery stenosis  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Dementia Alzheimer's type  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Subarachnoid haemorrhage  1  0/199 (0.00%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Reproductive system and breast disorders               
Ovarian cyst torsion  1  0/199 (0.00%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Pneumonia aspiration  1  0/199 (0.00%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Pneumothorax  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Skin and subcutaneous tissue disorders               
Acute febrile neutrophilic dermatosis  1  1/199 (0.50%)  0/66 (0.00%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Vascular disorders               
Aortic dissection  1  0/199 (0.00%)  0/66 (0.00%)  0/206 (0.00%)  1/68 (1.47%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Peripheral arterial occlusive disease  1  0/199 (0.00%)  1/66 (1.52%)  0/206 (0.00%)  0/68 (0.00%)  0/65 (0.00%)  0/200 (0.00%)  0/66 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
[1]
One treatment-emergent death occurred during treatment in NE-58095 DR 37.5 mg Once Monthly Following Breakfast group and is not related to study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NE-58095 IR 2.5 mg Once Daily on Awakening NE-58095 DR 25 mg Once Monthly on Awakening NE-58095 DR 25 mg Once Monthly Following Breakfast NE-58095 DR 25 mg Once Monthly 30 Min. After Breakfast NE-58095 DR 37.5 mg Once Monthly on Awakening NE-58095 DR 37.5 mg Once Monthly Following Breakfast NE-58095 DR 37.5 mg Once Monthly 30 Min. After Breakfast
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   128/199 (64.32%)   43/66 (65.15%)   132/206 (64.08%)   43/68 (63.24%)   46/65 (70.77%)   138/200 (69.00%)   42/66 (63.64%) 
Eye disorders               
Dry eye  1  2/199 (1.01%)  3/66 (4.55%)  3/206 (1.46%)  0/68 (0.00%)  4/65 (6.15%)  1/200 (0.50%)  0/66 (0.00%) 
Gastrointestinal disorders               
Abdominal discomfort  1  9/199 (4.52%)  2/66 (3.03%)  15/206 (7.28%)  8/68 (11.76%)  10/65 (15.38%)  22/200 (11.00%)  3/66 (4.55%) 
Constipation  1  10/199 (5.03%)  4/66 (6.06%)  12/206 (5.83%)  2/68 (2.94%)  4/65 (6.15%)  20/200 (10.00%)  2/66 (3.03%) 
Abdominal pain upper  1  3/199 (1.51%)  3/66 (4.55%)  14/206 (6.80%)  5/68 (7.35%)  4/65 (6.15%)  15/200 (7.50%)  6/66 (9.09%) 
Chronic gastritis  1  1/199 (0.50%)  0/66 (0.00%)  2/206 (0.97%)  1/68 (1.47%)  3/65 (4.62%)  2/200 (1.00%)  4/66 (6.06%) 
General disorders               
Pyrexia  1  1/199 (0.50%)  1/66 (1.52%)  9/206 (4.37%)  2/68 (2.94%)  3/65 (4.62%)  13/200 (6.50%)  1/66 (1.52%) 
Immune system disorders               
Seasonal allergy  1  1/199 (0.50%)  0/66 (0.00%)  2/206 (0.97%)  4/68 (5.88%)  0/65 (0.00%)  3/200 (1.50%)  1/66 (1.52%) 
Infections and infestations               
Nasopharyngitis  1  64/199 (32.16%)  19/66 (28.79%)  51/206 (24.76%)  25/68 (36.76%)  15/65 (23.08%)  42/200 (21.00%)  22/66 (33.33%) 
Cystitis  1  2/199 (1.01%)  2/66 (3.03%)  8/206 (3.88%)  1/68 (1.47%)  4/65 (6.15%)  10/200 (5.00%)  0/66 (0.00%) 
Gastroenteritis  1  1/199 (0.50%)  2/66 (3.03%)  5/206 (2.43%)  3/68 (4.41%)  2/65 (3.08%)  10/200 (5.00%)  1/66 (1.52%) 
Injury, poisoning and procedural complications               
Fall  1  21/199 (10.55%)  7/66 (10.61%)  13/206 (6.31%)  3/68 (4.41%)  3/65 (4.62%)  15/200 (7.50%)  5/66 (7.58%) 
Contusion  1  16/199 (8.04%)  5/66 (7.58%)  10/206 (4.85%)  1/68 (1.47%)  2/65 (3.08%)  13/200 (6.50%)  7/66 (10.61%) 
Ligament sprain  1  8/199 (4.02%)  2/66 (3.03%)  8/206 (3.88%)  0/68 (0.00%)  4/65 (6.15%)  8/200 (4.00%)  0/66 (0.00%) 
Arthropod sting  1  5/199 (2.51%)  2/66 (3.03%)  5/206 (2.43%)  1/68 (1.47%)  3/65 (4.62%)  10/200 (5.00%)  3/66 (4.55%) 
Musculoskeletal and connective tissue disorders               
Osteoarthritis  1  14/199 (7.04%)  1/66 (1.52%)  16/206 (7.77%)  5/68 (7.35%)  4/65 (6.15%)  11/200 (5.50%)  1/66 (1.52%) 
Arthralgia  1  4/199 (2.01%)  3/66 (4.55%)  13/206 (6.31%)  2/68 (2.94%)  2/65 (3.08%)  13/200 (6.50%)  3/66 (4.55%) 
Back pain  1  5/199 (2.51%)  4/66 (6.06%)  8/206 (3.88%)  1/68 (1.47%)  4/65 (6.15%)  16/200 (8.00%)  0/66 (0.00%) 
Periarthritis  1  8/199 (4.02%)  3/66 (4.55%)  5/206 (2.43%)  2/68 (2.94%)  4/65 (6.15%)  9/200 (4.50%)  1/66 (1.52%) 
Lumbar spinal stenosis  1  2/199 (1.01%)  0/66 (0.00%)  1/206 (0.49%)  4/68 (5.88%)  0/65 (0.00%)  3/200 (1.50%)  1/66 (1.52%) 
Nervous system disorders               
Headache  1  3/199 (1.51%)  1/66 (1.52%)  10/206 (4.85%)  4/68 (5.88%)  1/65 (1.54%)  5/200 (2.50%)  5/66 (7.58%) 
Respiratory, thoracic and mediastinal disorders               
Upper respiratory tract inflammation  1  9/199 (4.52%)  3/66 (4.55%)  10/206 (4.85%)  5/68 (7.35%)  4/65 (6.15%)  12/200 (6.00%)  2/66 (3.03%) 
Skin and subcutaneous tissue disorders               
Eczema  1  10/199 (5.03%)  3/66 (4.55%)  11/206 (5.34%)  2/68 (2.94%)  3/65 (4.62%)  12/200 (6.00%)  4/66 (6.06%) 
Vascular disorders               
Hypertension  1  2/199 (1.01%)  1/66 (1.52%)  7/206 (3.40%)  5/68 (7.35%)  2/65 (3.08%)  2/200 (1.00%)  4/66 (6.06%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
The collaborator company name EA Pharma Co., Ltd. has been changed from 1st April 2016. The legacy name was Ajinomoto Pharmaceutics Co., Ltd.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02063854     History of Changes
Obsolete Identifiers: NCT02066376
Other Study ID Numbers: CCT-401
JapicCTI-142440 ( Registry Identifier: JapicCTI )
U1111-1153-0440 ( Registry Identifier: WHO )
NE-58095DR/CCT-401 ( Other Identifier: Takeda ID )
First Submitted: February 12, 2014
First Posted: February 14, 2014
Results First Submitted: November 16, 2016
Results First Posted: February 23, 2017
Last Update Posted: February 23, 2017