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Efficacy and Safety of Intravenous Neridronic Acid in CRPS

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ClinicalTrials.gov Identifier: NCT03530345
Recruitment Status : Terminated (Sponsor decision)
First Posted : May 21, 2018
Results First Posted : August 6, 2020
Last Update Posted : August 6, 2020
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Complex Regional Pain Syndrome (CRPS)
Interventions Drug: Neridronic acid 100 mg
Drug: Placebo
Enrollment 182
Recruitment Details First participant enrollment on 30 May 2018. After a pooled interim analysis of primary endpoint data of studies KF7013-02 and KF7013-04 (NCT03560986), recruitment was stopped as interim results indicated futility. Last participant's last assessment was on 31 July 2019.
Pre-assignment Details 182 participants were enrolled (signed consent), 57 were allocated to treatment and received study medication. Of 125 participants not allocated, 95 did not meet inclusion/met exclusion criteria, 1 was lost to follow-up, 9 withdrew consent, 1 experienced technical problems, and 19 were not allocated for other reasons.
Arm/Group Title Neridronic Acid - Treatment Period A/B Placebo - Treatment Period A/B
Hide Arm/Group Description
  • Treatment Period A: Neridronic acid 100 mg - 4 intravenous infusions within 10 days; Follow-up Period 1 until 26 weeks.
  • Treatment Period B: Neridronic acid 100 mg - 4 intravenous infusions within 10 days; Follow-up Period 2 until 52 weeks.
  • Treatment Period A: Matching placebo - 4 intravenous infusions within 10 days; Follow-up Period 1 until 26 weeks.
  • Treatment Period B: Neridronic acid 100 mg - 4 intravenous infusions within 10 days; Follow-up Period 2 until 52 weeks.
Period Title: Treatment Period A/Follow-up Period 1
Started 28 29
Treatment Period A Completers 26 27
Completed [1] 7 7
Not Completed 21 22
Reason Not Completed
Lost to Follow-up             1             0
Withdrawal by Subject             3             1
Other reasons for discontinuation             17             21
[1]
Participants completing Follow-up Period 1.
Period Title: Treatment Period B/Follow-up Period 2
Started 5 [1] 7
Treatment Period B Completers 4 6
Completed [2] 0 0
Not Completed 5 7
Reason Not Completed
Other reasons for discontinuation             5             7
[1]
2 participants completed Treatment Period A/Follow-up Period 1 but were not allocated in Period B.
[2]
Participants completing Follow-up Period 2.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A Total
Hide Arm/Group Description Neridronic acid 400 mg administered by 4 intravenous infusions within 10 Days in Treatment Period A. Matching placebo administered by 4 intravenous infusions within 10 Days in Treatment Period A. Total of all reporting groups
Overall Number of Baseline Participants 28 29 57
Hide Baseline Analysis Population Description
Safety Set; all participants treated in Treatment Period A.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants 29 participants 57 participants
46.1  (11.0) 49.4  (12.1) 47.8  (11.6)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 29 participants 57 participants
< 18 years
0
   0.0%
0
   0.0%
0
   0.0%
From 18 to <65 years
28
 100.0%
25
  86.2%
53
  93.0%
From 65 to <85 years
0
   0.0%
4
  13.8%
4
   7.0%
85 years and above
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 29 participants 57 participants
Female
22
  78.6%
22
  75.9%
44
  77.2%
Male
6
  21.4%
7
  24.1%
13
  22.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 29 participants 57 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   7.1%
0
   0.0%
2
   3.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   7.1%
1
   3.4%
3
   5.3%
White
24
  85.7%
28
  96.6%
52
  91.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 29 participants 57 participants
New Zealand
0
   0.0%
1
   3.4%
1
   1.8%
South Korea
2
   7.1%
0
   0.0%
2
   3.5%
United States
22
  78.6%
22
  75.9%
44
  77.2%
Australia
0
   0.0%
1
   3.4%
1
   1.8%
Germany
1
   3.6%
0
   0.0%
1
   1.8%
Spain
3
  10.7%
5
  17.2%
8
  14.0%
Complex regional pain syndrome (CRPS) type   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants 29 participants 57 participants
CRPS Type I
25
  89.3%
21
  72.4%
46
  80.7%
CRPS Type II
3
  10.7%
8
  27.6%
11
  19.3%
[1]
Measure Description:

CRPS Type I: Occurs after a minor or major tissue injury without clinical signs of major peripheral nerve injury.

CRPS Type II: Occurs after an injury with clinical signs of major peripheral nerve injury.

Time since onset of CRPS symptoms  
Median (Inter-Quartile Range)
Unit of measure:  Months
Number Analyzed 28 participants 29 participants 57 participants
17.72
(7.60 to 22.02)
13.47
(8.20 to 18.87)
14.23
(7.80 to 20.80)
Time since diagnosis of CRPS  
Median (Inter-Quartile Range)
Unit of measure:  Months
Number Analyzed 28 participants 29 participants 57 participants
9.15
(4.82 to 16.07)
11.37
(3.30 to 17.87)
10.37
(4.30 to 16.67)
1.Primary Outcome
Title Change From Baseline to Week 12 in the Average Pain Intensity Score (Weekly Average of Pain Values Recorded Daily in the Electronic Diary)
Hide Description

In the Baseline Phase and in Treatment Period A/Follow-up Period 1, participants were asked to assessed their average CRPS-related pain on an 11-point numerical rating scale (NRS) - from 0 = "no pain" to 10 = "pain as bad as you can imagine" and report it once daily (in the evening, 24-hour recall) in an electronic diary.

Changes from baseline (average for the Baseline Phase) to the weekly average for Week 12 were calculated.

Time Frame From the Baseline Phase (Day -7 to Day -1) to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set; all participants treated in Treatment Period A with all data available at the time of last participant out following premature study termination.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A
Hide Arm/Group Description:
Neridronic acid 100 mg - 4 intravenous infusions within 10 Days
Matching placebo - 4 intravenous infusions within 10 Days
Overall Number of Participants Analyzed 28 29
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.23  (0.310) -0.16  (0.305)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Neridronic Acid - Treatment Period A, Placebo - Treatment Period A
Comments Mixed-effects model for repeated measures (MMRM) defined with baseline pain intensity as covariate, the factors geographic region, week, treatment and treatment-by-week as fixed effects, and an unstructured covariance matrix to model the covariance structure of the repeated measurements.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0111
Comments 2-sided p-value for testing superiority of neridronic acid 400 mg compared to placebo.
Method Mixed Models Analysis
Comments The degrees of freedom of the denominator are estimated using the Kenward-Roger approximation.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.07
Confidence Interval (2-Sided) 95%
-1.89 to -0.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.404
Estimation Comments The primary endpoint estimate was the least squares mean differences of change from baseline in pain NRS (electronic diary) at Week 12 between neridronate and Placebo.
2.Secondary Outcome
Title Change From Baseline to Week 26 in the Average Pain Intensity Recorded on the Tablet Computer.
Hide Description 11-point NRS - from 0 = "no pain" to 10 = "pain as bad as you can imagine" - reported at the visits on a tablet computer (24-hour recall). Changes from baseline to Week 26 were planned to be analyzed.
Time Frame From baseline (Visit 2 [Day 1]) to Visit 11 (Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected or analyzed because a confirmatory testing strategy was not performed as pre-specified in the protocol that secondary endpoints would only be tested if neridronic acid was superior to placebo on the primary outcome measure. A confirmatory or descriptive analysis was not performed due to early study termination.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A
Hide Arm/Group Description:
Neridronic acid 400 mg administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Matching placebo administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Pain Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Average Pain Intensity at Week 12, Recorded on the Tablet Computer.
Hide Description 11-point NRS - from 0 = "no pain" to 10 = "pain as bad as you can imagine" - reported at the visits on a tablet computer (24-hour recall). The number of participants with response at Week 12 was planned to be determined.
Time Frame From baseline (Visit 2 [Day 1]) to Visit 8 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected or analyzed because a confirmatory testing strategy was not performed as pre-specified in the protocol that secondary endpoints would only be tested if neridronic acid was superior to placebo on the primary outcome measure. A confirmatory or descriptive analysis was not performed due to early study termination.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A
Hide Arm/Group Description:
Neridronic acid 400 mg administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Matching placebo administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Pain Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Average Pain Intensity at Week 26, Recorded on the Tablet Computer.
Hide Description 11-point NRS - from 0 = "no pain" to 10 = "pain as bad as you can imagine" - reported at the visits on a tablet computer (24-hour recall). The number of participants with response at Week 26 was planned to be determined.
Time Frame From baseline (Visit 2 [Day 1]) to Visit 11 (Week 26)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected or analyzed because a confirmatory testing strategy was not performed as pre-specified in the protocol that secondary endpoints would only be tested if neridronic acid was superior to placebo on the primary outcome measure. A confirmatory or descriptive analysis was not performed due to early study termination.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A
Hide Arm/Group Description:
Neridronic acid 400 mg administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Matching placebo administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Change From Baseline to Week 12 in the Pain Intensity Level of Dynamic Mechanical Allodynia (DMA).
Hide Description Dynamic mechanical allodynia: a tactile stimulus is applied in a single sweeping motion (1 cm to 2 cm length) on the skin on the affected limb. The participants are asked to judge the stimulus intensity by means of an NRS (0 to 10). "0" in this case means "no pain". Each "pricking", "stinging" or "burning" sensation is defined as a painful sensation, which should always be evaluated by giving a value greater than "0". "10" corresponds to the individual maximum pain imaginable. Change from baseline was planned to analyzed.
Time Frame From baseline (Visit 2 [Day 1]) to Visit 8 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected or analyzed because a confirmatory testing strategy was not performed as pre-specified in the protocol that secondary endpoints would only be tested if neridronic acid was superior to placebo on the primary outcome measure. A confirmatory or descriptive analysis was not performed due to early study termination.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A
Hide Arm/Group Description:
Neridronic acid 400 mg administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Matching placebo administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Change From Baseline to Week 12 in the Pressure Pain Threshold (PPT) Ratio for the Thenar Muscle/Abductor Hallucis Muscle.
Hide Description

Pressure pain threshold: using a pressure algometer (contact area 1 cm2), the threshold for pressure-induced pain is measured on the thenar muscle/abductor hallucis muscle in 3 series of slowly increasing stimulus intensities (at a rate of about 50 kPa/s). The threshold is then determined as the arithmetic mean of the 3 series (in kPa).

The ratio of the thresholds of the affected limb versus the unaffected limb was planned to be calculated.

Time Frame From baseline (Visit 2 [Day 1]) to Visit 8 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected or analyzed because a confirmatory testing strategy was not performed as pre-specified in the protocol that secondary endpoints would only be tested if neridronic acid was superior to placebo on the primary outcome measure. A confirmatory or descriptive analysis was not performed due to early study termination.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A
Hide Arm/Group Description:
Neridronic acid 400 mg administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Matching placebo administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Change From Baseline to Week 12 in the Ratio of the Figure of Eight Measurements of the Affected Limb Versus the Unaffected Limb.
Hide Description

In participants with the CRPS sign of edema on the CRPS severity score at baseline, circumference of the hand or foot will be measured by the investigator with measurement tape using the figure-of-eight method at both the affected limb and the contralateral unaffected limb. Each measurement will be performed 3 times. The average of the 3 measurements will be used for further analysis.

The ratio of the averages of the affected limb versus the unaffected limb was planned to be calculated and used for the determination of the change from baseline.

Time Frame From baseline (Visit 2 [Day 1]) to Visit 8 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected or analyzed because a confirmatory testing strategy was not performed as pre-specified in the protocol that secondary endpoints would only be tested if neridronic acid was superior to placebo on the primary outcome measure. A confirmatory or descriptive analysis was not performed due to early study termination.
Arm/Group Title Neridronic Acid - Treatment Period A Placebo - Treatment Period A
Hide Arm/Group Description:
Neridronic acid 400 mg administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Matching placebo administered by 4 intravenous infusions within 10 Days in Treatment Period A.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events were documented from the time of enrollment (i.e., the time the informed consent form was signed) up to the time of the last protocol scheduled contact, i.e., date of last visit/contact (could be a phone call, e.g., in case of withdrawal). Only treatment emergent adverse events (TEAEs, i.e., those reported from baseline (after first administration of study medication) are reported in the tables below.
Adverse Event Reporting Description

Participants with TEAEs may be presented in 2 of 6 reporting groups depending on the time the TEAEs were reported.

  • Treatment Period A/Follow-up Period 1 (TPA): Baseline to Week 26 (Placebo or neridronic acid).
  • Treatment Period B/Follow-up Period 2 (TPB): Week 26 to Week 52 (follow-up without study medication administration) or Week 26 to Week 52 (participants with neridronic acid treatment after placebo and those receiving re-treatment with neridronic acid).
 
Arm/Group Title Baseline to Week 26: Placebo TPA Baseline to Week 26: Neridronic Acid TPA Week 26 to Week 52: Placebo TPA Week 26 to Week 52: Placebo TPA, Neridronic Acid TPB Week 26 to Week 52: Neridronic Acid TPA Week 26 to Week 52: Neridronic Acid TPA, Neridronic Acid TPB
Hide Arm/Group Description In Treatment Period A, participants received matching placebo - 4 intravenous infusions within 10 Days; Follow-up Period 1 until 26 weeks. In Treatment Period A, participants received neridronic acid 100 mg - 4 intravenous infusions within 10 days; Follow-up Period 1 until 26 weeks. Participants with placebo treatment in Treatment Period A/Follow-up Period 1 were followed up without administration of study medication until 52 weeks in Follow-up Period 2. Participants who had completed treatment with placebo in Treatment Period A/Follow-up Period 1 received neridronic acid treatment (100 mg - 4 intravenous infusions within 10 days) in Treatment Period B/Follow-up Period 2 until 52 weeks. Participants who had completed treatment with neridronic acid treatment in Treatment Period A/Follow-up Period 1 were followed up without administration of study medication until 52 weeks in Follow-up Period 2. Participants who had completed treatment with neridronic acid in Treatment Period A/Follow-up Period 1 received re-treatment with neridronic acid 100 mg - 4 intravenous infusions within 10 days; Follow-up Period 2 until 52 weeks.
All-Cause Mortality
Baseline to Week 26: Placebo TPA Baseline to Week 26: Neridronic Acid TPA Week 26 to Week 52: Placebo TPA Week 26 to Week 52: Placebo TPA, Neridronic Acid TPB Week 26 to Week 52: Neridronic Acid TPA Week 26 to Week 52: Neridronic Acid TPA, Neridronic Acid TPB
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)      0/28 (0.00%)      0/22 (0.00%)      0/7 (0.00%)      0/23 (0.00%)      0/5 (0.00%)    
Hide Serious Adverse Events
Baseline to Week 26: Placebo TPA Baseline to Week 26: Neridronic Acid TPA Week 26 to Week 52: Placebo TPA Week 26 to Week 52: Placebo TPA, Neridronic Acid TPB Week 26 to Week 52: Neridronic Acid TPA Week 26 to Week 52: Neridronic Acid TPA, Neridronic Acid TPB
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/29 (0.00%)      2/28 (7.14%)      0/22 (0.00%)      0/7 (0.00%)      0/23 (0.00%)      0/5 (0.00%)    
Gastrointestinal disorders             
Abdominal pain upper  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Psychiatric disorders             
Suicidal ideation  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Baseline to Week 26: Placebo TPA Baseline to Week 26: Neridronic Acid TPA Week 26 to Week 52: Placebo TPA Week 26 to Week 52: Placebo TPA, Neridronic Acid TPB Week 26 to Week 52: Neridronic Acid TPA Week 26 to Week 52: Neridronic Acid TPA, Neridronic Acid TPB
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/29 (51.72%)      16/28 (57.14%)      0/22 (0.00%)      3/7 (42.86%)      1/23 (4.35%)      0/5 (0.00%)    
Cardiac disorders             
Atrial flutter  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Eye disorders             
Dry eye  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Eye pain  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Gastrointestinal disorders             
Abdominal pain  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Abdominal pain upper  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Burning mouth syndrome  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Constipation  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Dental paraesthesia  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Diarrhoea  1  1/29 (3.45%)  1 2/28 (7.14%)  2 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Gastritis  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Gastrooesophageal reflux disease  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Gingival discomfort  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Nausea  1  4/29 (13.79%)  4 2/28 (7.14%)  2 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Vomiting  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
General disorders             
Acute phase reaction  1  0/29 (0.00%)  0 4/28 (14.29%)  7 0/22 (0.00%)  0 3/7 (42.86%)  6 0/23 (0.00%)  0 0/5 (0.00%)  0
Chest pain  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Fatigue  1  2/29 (6.90%)  5 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Feeling cold  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Influenza like illness  1  2/29 (6.90%)  2 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Oedema peripheral  1  0/29 (0.00%)  0 2/28 (7.14%)  5 0/22 (0.00%)  0 1/7 (14.29%)  1 0/23 (0.00%)  0 0/5 (0.00%)  0
Pain  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Pyrexia  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Infections and infestations             
Bronchitis  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Nasopharyngitis  1  0/29 (0.00%)  0 2/28 (7.14%)  2 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Pharyngitis streptococcal  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Sinusitis  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Urinary tract infection  1  0/29 (0.00%)  0 0/28 (0.00%)  0 0/22 (0.00%)  0 1/7 (14.29%)  1 0/23 (0.00%)  0 0/5 (0.00%)  0
Injury, poisoning and procedural complications             
Epicondylitis  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Skin laceration  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Fall  1  0/29 (0.00%)  0 0/28 (0.00%)  0 0/22 (0.00%)  0 1/7 (14.29%)  1 0/23 (0.00%)  0 0/5 (0.00%)  0
Investigations             
Aspartate aminotransferase increased  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Lipase increased  1  1/29 (3.45%)  2 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Metabolism and nutrition disorders             
Hypercalcaemia  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthralgia  1  1/29 (3.45%)  2 0/28 (0.00%)  0 0/22 (0.00%)  0 1/7 (14.29%)  1 0/23 (0.00%)  0 0/5 (0.00%)  0
Joint instability  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Musculoskeletal pain  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Myalgia  1  0/29 (0.00%)  0 1/28 (3.57%)  2 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Pain in extremity  1  2/29 (6.90%)  2 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Periarthritis  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Synovitis  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Back pain  1  0/29 (0.00%)  0 0/28 (0.00%)  0 0/22 (0.00%)  0 1/7 (14.29%)  1 0/23 (0.00%)  0 0/5 (0.00%)  0
Nervous system disorders             
Dizziness  1  0/29 (0.00%)  0 2/28 (7.14%)  2 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Headache  1  3/29 (10.34%)  6 2/28 (7.14%)  2 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Migraine  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Occipital neuralgia  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Paraesthesia  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Psychiatric disorders             
Anxiety  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Depression  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Insomnia  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Renal and urinary disorders             
Haematuria  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Cough  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Pulmonary embolism  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Skin and subcutaneous tissue disorders             
Blister  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Night sweats  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Pruritus  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Rash  1  1/29 (3.45%)  1 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Surgical and medical procedures             
Foot operation  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Medical device removal  1  0/29 (0.00%)  0 1/28 (3.57%)  1 0/22 (0.00%)  0 0/7 (0.00%)  0 0/23 (0.00%)  0 0/5 (0.00%)  0
Medical device implantation  1  0/29 (0.00%)  0 0/28 (0.00%)  0 0/22 (0.00%)  0 0/7 (0.00%)  0 1/23 (4.35%)  1 0/5 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
A pre-specified interim analysis was conducted on pooled primary endpoint data of studies KF7013-02 and KF7013-04 (NCT03560986). The interim analysis indicated futility (neridronate unlikely to be superior to placebo) and both studies were stopped.
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 sponsor reserves the right to review any proposed full publication or poster or presentation of the results of this study by the coordinating or other investigator before they are submitted for publication or public disclosure. Neither the sponsor nor the coordinating investigator has the right to prohibit publication or public disclosure. Publication or public disclosure can be postponed for patent purposes.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director Clinical Trials
Organization: Grünenthal GmbH
Phone: +49 241 569 ext 3223
EMail: Clinical-Trials@grunenthal.com
Layout table for additonal information
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT03530345    
Other Study ID Numbers: KF7013-02
2016-003833-91 ( EudraCT Number )
U1111-1187-8036 ( Other Identifier: World Health Organization )
First Submitted: May 7, 2018
First Posted: May 21, 2018
Results First Submitted: June 23, 2020
Results First Posted: August 6, 2020
Last Update Posted: August 6, 2020