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One Week Parathyroid Hormone-related Protein (PTHrP) IV Dose Escalation Study

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: NCT00580788
Recruitment Status : Completed
First Posted : December 27, 2007
Results First Posted : February 11, 2016
Last Update Posted : February 11, 2016
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Mara Horwitz, University of Pittsburgh

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: Single (Participant)
Conditions Osteoporosis
Humoral Hypercalcemia of Malignancy
Hyperparathyroidism
Intervention Drug: PTHrP (1-36)
Enrollment 14
Recruitment Details 24 subjects were screened and 14 were randomized in the study. Data from 2 subjects was not included in the analysis as there were not enough subjects in that group for analysis. 12 subjects were analyzed.
Pre-assignment Details  
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description PTHrP(1-36) 2 picomoles/kg/hr PTHrP(1-36) 4 picomoles/kg/hr PTHrP (1-36) 5 pmol/kg/hr PTHrP (1-36) 6 picomoles/kg/hr
Period Title: Overall Study
Started 3 6 3 2
Completed 3 6 3 1 [1]
Not Completed 0 0 0 1
Reason Not Completed
Adverse Event             0             0             0             1
[1]
One subject was stopped early for hypertension. One subject completed but was not analyzed.
Arm/Group Title Group 1 Group 2 Group 3 Group 4 Total
Hide Arm/Group Description PTHrP(1-36) 2 picomoles/kg/hr for one week. PTHrP(1-36) 4 picomoles/kg/hr for one week. PTHrP(1-36) 5 picomoles/kg/hr for one week. PTHrP(1-36) 6 picomoles/kg/hr for one week. Total of all reporting groups
Overall Number of Baseline Participants 3 6 3 2 14
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 3 participants 2 participants 14 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
 100.0%
6
 100.0%
3
 100.0%
2
 100.0%
14
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 3 participants 2 participants 14 participants
Female
2
  66.7%
3
  50.0%
2
  66.7%
0
   0.0%
7
  50.0%
Male
1
  33.3%
3
  50.0%
1
  33.3%
2
 100.0%
7
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 6 participants 3 participants 2 participants 14 participants
3 6 3 2 14
1.Primary Outcome
Title Dose Limiting Toxicity (DLT)
Hide Description DLT was defined as achieving one major criterion or two minor criteria rated at ≥ 2 on a scale of 0-5. The major criteria were defined as symptomatic orthostatic hypotension (systolic BP fall >30 mm/hg), tachycardia (pulse > 120), hypertension (systolic BP >160 mm/hg on 2 occasions), hypercalcemia (serum calcium ≥ 12 mg/dl), and hypophosphatemia (serum phosphorous < 1.5 mg/dl). Minor criteria included symptoms such as flushing, nausea, abdominal or muscle cramps, dizziness, lightheadedness, palpitations, etc.
Time Frame 12 hours after the infusion was started then q 8 hours for 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week
PTHrP(1-36) 5 picomoles/kg/hr for one week
PTHrP(1-36) 6 picomoles/kg/hr for one week
Overall Number of Participants Analyzed 3 6 3 2
Measure Type: Number
Unit of Measure: participants
0 0 2 2
2.Primary Outcome
Title Total Serum Calcium
Hide Description mg/dl
Time Frame 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr
PTHrP(1-36) 4 picomoles/kg/hr
PTHrP (1-36) 5 pmol/kg/hr
PTHrP (1-36) 6 picomoles/kg/hr
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: mg/dl
baseline 9.37  (0.07) 9.58  (0.12) 9.2  (0.25)
11P DAY 1 9.67  (0.09) 9.80  (0.16) 9.67  (0.20)
7A DAY 2 9.4  (0.17) 10.05  (0.19) 10.17  (0.20)
3P DAY 2 9.57  (0.09) 10.28  (0.14) 10.47  (0.30)
11P DAY 2 9.67  (0.09) 10.32  (0.14) 10.23  (0.26)
7A DAY 3 9.6  (0.10) 10.40  (0.18) 10.73  (0.57)
3P DAY 3 9.73  (0.09) 10.42  (0.14) 10.67  (0.27)
11P DAY 3 9.40  (0.17) 9.73  (0.10) 9.93  (0.38)
7A DAY 4 9.47  (0.03) 10.00  (0.24) 10.3  (0.23)
3P DAY 4 9.40  (0.17) 9.92  (0.21) 10.33  (0.34)
11P DAY 4 9.37  (0.09) 9.48  (0.11) 10.00  (0.15)
7A DAY 5 9.30  (0.12) 9.62  (0.12) 10.53  (0.15)
3P DAY 5 9.50  (0.15) 9.83  (0.20) 10.27  (0.44)
11P DAY 5 9.43  (0.09) 9.45  (0.13) 9.80  (0.20)
7A DAY 6 9.57  (0.07) 9.83  (0.20) 10.53  (0.22)
3P DAY 6 9.43  (0.15) 10.08  (0.12) 10.83  (0.27)
11P DAY 6 9.43  (0.13) 9.67  (0.21) 10.43  (0.47)
7A DAY 7 9.40  (0.10) 10.13  (0.28) 10.90  (0.46)
3P DAY 7 9.70  (0.15) 10.22  (0.32) 10.70  (0.46)
11P DAY 7 9.60  (0.15) 10.27  (0.28) 10.73  (0.50)
7A DAY 8 9.83  (0.13) 10.67  (0.40) 11.17  (0.35)
FOLLOW-UP 9.33  (0.07) 9.80  (0.12) 9.17  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value <0.0001
Comments The reported p-value corresponds to the increase over time for the PTHrP 4 pmol group.
Method Mixed Models Analysis
Comments Value The level of statistical significance was set at .05 (two-tailed)
3.Primary Outcome
Title Ionized Serum Calcium
Hide Description mg/dl
Time Frame 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr
PTHrP(1-36) 4 picomoles/kg/hr
PTHrP (1-36) 5 pmol/kg/hr
PTHrP (1-36) 6 picomoles/kg/hr
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: mg/dl
baseline 4.79  (0.03) 4.72  (0.08) 4.55  (0.15)
11P DAY 1 4.51  (0.05) 4.77  (0.08) 4.75  (0.04)
7A DAY 2 4.77  (0.07) 4.98  (0.10) 5.07  (0.07)
3P DAY 2 4.52  (0.02) 4.99  (0.06) 5.07  (0.06)
11P DAY 2 4.48  (0.08) 5.04  (0.07) 4.84  (0.00)
7A DAY 3 4.77  (0.15) 5.31  (0.08) 5.25  (0.13)
3P DAY 3 4.73  (0.11) 4.99  (0.10) 4.91  (0.16)
11P DAY 3 4.41  (0.15) 4.58  (0.15) 4.83  (0.14)
7A DAY 4 4.75  (0.14) 4.90  (0.13) 5.11  (0.09)
3P DAY 4 4.45  (0.16) 4.68  (0.14) 4.72  (0.17)
11P DAY 4 4.47  (0.07) 4.46  (0.12) 4.69  (0.06)
7A DAY 5 4.71  (0.07) 4.82  (0.09) 4.97  (0.12)
3P DAY 5 4.61  (0.20) 4.67  (0.12) 4.87  (0.40)
11P DAY 5 4.60  (0.13) 4.58  (0.07) 4.79  (0.09)
7A DAY 6 4.63  (0.03) 4.77  (0.10) 5.25  (0.09)
3P DAY 6 4.72  (0.13) 4.83  (0.07) 5.35  (0.03)
11P DAY 6 4.32  (0.06) 4.72  (0.09) 5.19  (0.21)
7A DAY 7 4.55  (0.22) 5.01  (0.09) 5.55  (0.27)
3P DAY 7 4.84  (0.16) 5.04  (0.17) 5.25  (0.31)
11P DAY 7 4.56  (0.12) 4.87  (0.19) 5.24  (0.02)
7A DAY 8 5.00  (0.11) 5.43  (0.18) 5.69  (0.10)
FOLLOW-UP 4.68  (0.08) 4.83  (0.05) 4.80  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value <0.0001
Comments The reported p-value corresponds to the increase over time for the PTHrP 4 pmol group.
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
4.Primary Outcome
Title Serum Phosphorous
Hide Description mg/dl
Time Frame 12 hours after the infusion was started then q 8 hours for 7 days, Follow-up 1 week after infusion complete
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr
PTHrP(1-36) 4 picomoles/kg/hr
PTHrP (1-36) 5 pmol/kg/hr
PTHrP (1-36) 6 picomoles/kg/hr
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: mg/dl
baseline 3.55  (0.15) 3.63  (0.14) 3.55  (0.45)
11P DAY 1 3.87  (0.26) 3.90  (0.16) 4.03  (0.12)
7A DAY 2 4.07  (0.15) 4.20  (0.15) 3.63  (0.44)
3P DAY 2 3.63  (0.33) 3.50  (0.23) 3.70  (0.20)
11P DAY 2 4.13  (0.29) 3.52  (0.19) 3.63  (0.19)
7A DAY 3 3.90  (0.26) 3.77  (0.19) 3.43  (0.39)
3P DAY 3 3.53  (0.24) 3.53  (0.18) 3.60  (0.23)
11P DAY 3 4.03  (0.26) 3.58  (0.17) 3.70  (0.15)
7A DAY 4 4.07  (0.22) 3.90  (0.13) 3.30  (0.40)
3P DAY 4 3.90  (0.10) 3.37  (0.20) 3.33  (0.32)
11P DAY 4 3.67  (0.28) 3.48  (0.14) 3.63  (0.27)
7A DAY 5 3.87  (0.19) 4.02  (0.14) 3.20  (0.30)
3P DAY 5 3.57  (0.29) 3.35  (0.20) 3.10  (0.21)
11P DAY 5 3.93  (0.23) 3.45  (0.20) 3.87  (0.32)
7A DAY 6 4.00  (0.06) 4.00  (0.10) 3.63  (0.35)
3P DAY 6 3.67  (0.03) 3.80  (0.14) 3.73  (0.19)
11P DAY 6 3.93  (0.18) 3.90  (0.10) 3.93  (0.09)
7A DAY 7 4.30  (0.10) 4.28  (0.12) 3.73  (0.38)
3P DAY 7 4.07  (0.09) 3.62  (0.20) 3.50  (0.20)
11P DAY 7 4.20  (0.26) 3.62  (0.19) 3.60  (0.30)
7A DAY 8 4.43  (0.15) 4.10  (0.10) 3.40  (0.23)
FOLLOW-UP 3.57  (0.38) 3.48  (0.26) 3.87  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value >.05
Comments The reported p-value corresponds to change over time from baseline for all Arms/groups
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
5.Secondary Outcome
Title 1,25 Vitamin D
Hide Description pg/ml
Time Frame Baseline and Daily through day 8 then at follow-up visit
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week.
PTHrP(1-36) 5 picomoles/kg/hr for one week.
PTHrP(1-36) 6 picomoles/kg/hr for one week.
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: pg/ml
baseline 34.13  (3.03) 45.08  (4.24) 39.0  (4.09)
Day 2 38.40  (5.12) 45.88  (1.53) 39.77  (2.69)
Day 3 30.13  (4.57) 36.58  (4.17) 36.73  (2.75)
Day 4 32.23  (2.32) 40.38  (4.18) 35.17  (2.63)
Day 5 32.27  (1.80) 46.40  (6.12) 32.07  (3.79)
Day 6 42.77  (4.23) 34.90  (4.91) 35.37  (2.98)
Day 7 40.53  (4.38) 37.12  (3.58) 31.17  (6.84)
Day 8 32.37  (3.17) 33.43  (3.13) 30.63  (4.79)
follow-up 40.10  (4.01) 45.78  (4.72) 36.33  (2.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value >0.05
Comments The reported p-value corresponds to change over time for the PTHrP 2 and PTHrP 5 pmol groups
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 2
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value 0.01
Comments the reported p value corresponds to a decrease by Day 8 compared to baseline in the PTHrP 4 pmol group
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
6.Secondary Outcome
Title 24 Hour Urine Calcium
Hide Description mg/gm creatinine collected on day 7 of PTHrP infusion
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week
PTHrP(1-36) 5 picomoles/kg/hr for one week
PTHrP(1-36) 6 picomoles/kg/hr for one week
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: mg/gm creatinine
121.64  (9.87) 283.43  (30.93) 320.23  (41.32)
7.Secondary Outcome
Title Tubular Maximum of Phosphorous (TmP/GFR)
Hide Description mg/dl calculated from daily second morning void
Time Frame daily
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week
PTHrP(1-36) 5 picomoles/kg/hr for one week
PTHrP(1-36) 6 picomoles/kg/hr for one week
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: mg/dl
Baseline 3.43  (0.26) 3.91  (0.23) 3.38  (0.35)
Day 2 4.48  (0.20) 4.08  (0.23) 3.47  (0.46)
Day 3 4.28  (0.30) 3.74  (0.26) 3.25  (0.50)
Day 4 4.42  (0.31) 3.75  (0.31) 3.15  (0.45)
Day 5 4.43  (0.02) 3.95  (0.34) 3.37  (0.45)
Day 6 4.90  (0.08) 3.98  (0.11) 3.38  (0.35)
Day 7 4.15  (0.08) 3.98  (0.19) 2.95  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value 0.61
Comments The reported p-value corresponds to all Arms/Groups at all time points compared to baseline
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
8.Secondary Outcome
Title Serum Amino-terminal Telopeptide of Collagen -1 (sNTX)
Hide Description % change from baseline
Time Frame Baseline, Daily, and 1 week follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week.
PTHrP(1-36) 5 picomoles/kg/hr for one week.
PTHrP(1-36) 6 picomoles/kg/hr for one week.
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: % change
baseline 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Day 2 32.86  (23.41) 87.75  (18.79) 54.21  (10.64)
Day 3 26.73  (23.19) 91.53  (28.94) 88.51  (19.99)
Day 4 28.32  (20.26) 90.86  (32.25) 89.57  (20.22)
Day 5 41.29  (20.06) 82.36  (20.62) 116.58  (13.85)
Day 6 11.41  (12.63) 123.08  (28.62) 150.82  (48.26)
Day 7 35.04  (21.44) 161.55  (41.54) 176.42  (50.08)
Day 8 65.77  (30.43) 214.90  (59.26) 108.69  (34.29)
follow-up -14.95  (2.97) -3.33  (6.68) -9.02  (7.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value <.008
Comments The reported p-value corresponds to the % increase compared to baseline in all Arms/groups on Days 2-8.
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value >0.05
Comments The reported p-value corresponds the the % change from baseline at follow-up in all Arms/groups
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
9.Secondary Outcome
Title Serum Carboxy-terminal Telopeptide of Collagen -1 (sCTX)
Hide Description % change from baseline
Time Frame Baseline, Daily, and 1 week follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week.
PTHrP(1-36) 5 picomoles/kg/hr for one week.
PTHrP(1-36) 6 picomoles/kg/hr for one week.
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: % change
baseline 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Day 2 59.78  (18.14) 147.12  (40.72) 105.06  (11.54)
Day 3 66.67  (32.24) 180.27  (44.45) 148.45  (36.80)
Day 4 71.19  (18.88) 167.01  (47.01) 165.16  (40.29)
Day 5 79.39  (23.89) 167.27  (25.30) 174.58  (47.26)
Day 6 74.09  (26.72) 239.51  (49.42) 230.42  (54.10)
Day 7 109.27  (29.39) 283.15  (65.65) 267.89  (104.52)
Day 8 110.61  (30.92) 368.31  (93.63) 140.58  (78.58)
follow-up -35.73  (11.53) -8.60  (11.15) -41.33  (20.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value <.0001
Comments The reported p-value corresponds to % change (increase) from baseline in all Arms/groups at Days 2-8.
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value >0.05
Comments The reported p-value corresponds to the % change from baseline at follow-up in all Arms/groups
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
10.Secondary Outcome
Title Amino-terminal Peptides of Procollagen 1 (P1NP)
Hide Description % change from baseline
Time Frame Baseline, Daily, and 1 week follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week.
PTHrP(1-36) 5 picomoles/kg/hr for one week.
PTHrP(1-36) 6 picomoles/kg/hr for one week.
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: % change
baseline 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Day 2 -1.05  (4.95) -17.49  (5.93) -23.88  (6.05)
Day 3 -6.83  (2.78) -30.44  (7.10) -37.77  (6.56)
Day 4 -12.16  (0.57) -25.66  (9.55) -39.44  (4.46)
Day 5 -5.63  (2.27) -21.27  (8.01) -45.04  (3.07)
Day 6 -8.42  (5.07) -31.71  (7.50) -39.55  (1.75)
Day 7 -12.59  (6.17) -30.98  (8.87) -39.88  (2.78)
Day 8 -16.03  (5.03) -36.60  (9.64) -38.53  (3.40)
follow-up -7.12  (2.29) 0.60  (9.58) 46.67  (17.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value <.0001
Comments the reported p-value corresponds to % decrease compared to baseline at Days 2-8 in all Arms/groups
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value 0.01
Comments the reported p-value corresponds to % change from baseline at the follow-up visit in all Arms/groups
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
11.Secondary Outcome
Title Bone Specific Alkaline Phosphatase (BSAP)
Hide Description % change from baseline
Time Frame Baseline, Daily, and 1 week follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week.
PTHrP(1-36) 5 picomoles/kg/hr for one week.
PTHrP(1-36) 6 picomoles/kg/hr for one week.
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: % change
baseline 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Day 2 -12.53  (8.60) -1.17  (4.10) 24.54  (7.01)
Day 3 -6.35  (4.84) -1.44  (3.07) 34.77  (6.53)
Day 4 -5.82  (1.58) -3.79  (4.65) 19.49  (8.23)
Day 5 -0.33  (0.33) -9.64  (4.73) 13.61  (9.76)
Day 6 -8.16  (9.32) -10.88  (4.04) 9.02  (8.94)
Day 7 -11.91  (10.38) -16.78  (2.58) 9.86  (4.01)
Day 8 -7.80  (8.66) -14.01  (3.72) 15.27  (11.63)
follow-up -1.25  (2.70) 6.16  (3.81) 18.23  (2.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value 0.001
Comments the reported p-value correspond to the decrease compared to baseline over time in the PTHrP 4 pmol group.
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value .01
Comments the reported p=value corresponds to % change compared to baseline at follow-up in all Arms/groups
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
12.Secondary Outcome
Title Parathyroid Hormone (1-84)
Hide Description pg/ml
Time Frame Baseline and Daily
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week.
PTHrP(1-36) 5 picomoles/kg/hr for one week.
PTHrP(1-36) 6 picomoles/kg/hr for one week.
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: pg/ml
baseline 42.97  (2.86) 30.70  (5.56) 48.27  (15.93)
Day 2 23.47  (1.48) 7.82  (1.50) 3.60  (0.50)
Day 3 21.43  (3.65) 5.23  (1.75) 3.00  (0.00)
Day 4 26.77  (3.24) 7.88  (3.21) 3.00  (0.00)
Day 5 22.37  (5.10) 7.54  (1.80) 3.00  (0.00)
Day 6 21.13  (5.88) 6.57  (2.24) 3.00  (0.00)
Day 7 19.40  (4.03) 5.67  (1.20) 3.00  (0.00)
Day 8 12.60  (3.58) 3.00  (0.00) 3.00  (0.00)
follow-up 56.37  (5.18) 31.60  (2.63) 44.20  (10.87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1, Group 2, Group 3
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value <0.05
Comments the reported p-values correspond to the decrease compared to baseline in all arms/groups at Days 2-8
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
13.Secondary Outcome
Title Fractional Excretion of Calcium
Hide Description % calculated from daily second morning void
Time Frame daily
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description:
PTHrP(1-36) 2 picomoles/kg/hr for one week.
PTHrP(1-36) 4 picomoles/kg/hr for one week
PTHrP(1-36) 5 picomoles/kg/hr for one week
PTHrP(1-36) 6 picomoles/kg/hr for one week
Overall Number of Participants Analyzed 3 6 3 0
Mean (Standard Error)
Unit of Measure: % of filtered load
Baseline 1.93  (0.91) 2.57  (0.73) 2.38  (0.59)
Day 2 1.31  (0.59) 2.26  (0.46) 4.11  (2.42)
Day 3 1.07  (0.51) 2.85  (0.61) 3.27  (0.45)
Day 4 1.57  (0.25) 2.79  (0.76) 2.14  (0.40)
Day 5 3.05  (0.70) 2.05  (0.46) 3.12  (0.46)
Day 6 3.37  (0.67) 2.75  (0.25) 5.42  (2.23)
Day 7 2.72  (0.28) 3.94  (0.38) 4.13  (0.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The study was designed as a standard dose-escalation study, dose-finding pilot study. The primary outcome measures were safety (hypercalcemia, hypophosphatemia and symptoms/hemodynamic measurements). A modified Fibronacci dose-escalation scheme was employed.
Statistical Test of Hypothesis P-Value .002
Comments the reported p-value corresponds to the increase comapred to baseline over time (days 2-8) in the PTHrP 4 pmol group
Method Mixed Models Analysis
Comments The level of statistical significance was set at .05 (two-tailed)
Time Frame Subjects were systematically assessed every 8 hours for adverse events
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1 Group 2 Group 3 Group 4
Hide Arm/Group Description PTHrP(1-36) 2 picomoles/kg/hr for one week. PTHrP(1-36) 4 picomoles/kg/hr for one week. PTHrP(1-36) 5 picomoles/kg/hr for one week. PTHrP(1-36) 6 picomoles/kg/hr for one week.
All-Cause Mortality
Group 1 Group 2 Group 3 Group 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Group 1 Group 2 Group 3 Group 4
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/6 (0.00%)      0/3 (0.00%)      0/2 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1 Group 2 Group 3 Group 4
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/6 (0.00%)      1/3 (33.33%)      2/2 (100.00%)    
Endocrine disorders         
hypercalcemia   0/3 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1 1/2 (50.00%)  1
hypertension   0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/2 (50.00%)  1
migraine   0/3 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1 0/2 (0.00%)  0
lightheaded   0/3 (0.00%)  0 0/6 (0.00%)  0 1/3 (33.33%)  1 0/2 (0.00%)  0
tachycardia   0/3 (0.00%)  0 0/6 (0.00%)  0 0/3 (0.00%)  0 1/2 (50.00%)  1
Indicates events were collected by systematic assessment
Small number of subjects in each group Study limited to Caucasians Only one timepoint for follow-up was measure Study did not include saline infused controls
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mara J Horwitz, MD
Organization: University of Pittsburgh
Phone: 4126922848
EMail: horwitz@pitt.edu
Publications:
Layout table for additonal information
Responsible Party: Mara Horwitz, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00580788     History of Changes
Other Study ID Numbers: PRO07040081
R01DK073039 ( U.S. NIH Grant/Contract )
First Submitted: December 20, 2007
First Posted: December 27, 2007
Results First Submitted: April 25, 2014
Results First Posted: February 11, 2016
Last Update Posted: February 11, 2016