Trial Outcomes & Findings for A Study of Relative Bioavailability of a New Formulation Compared With the Approved Formulation of rhPTH [1-84] and to Find Out Dose Linearity of the New Formulation in Healthy Adults (NCT NCT05137730)
NCT ID: NCT05137730
Last Updated: 2023-12-15
Results Overview
AUClast was a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
96 participants
Primary outcome timeframe
Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dose
Results posted on
2023-12-15
Participant Flow
This study was conducted at single site in the United States of America from 29 November 2021 (first participant first visit) and 15 April 2022 (last participant last visit).
Study was conducted in 2 parts: Part 1 (To Assess Relative Bioavailability) and Part 2 (Dose Linearity). A total of 96 participants (84 participants in Part I and 12 participants in Part II) were enrolled in this study.
Participant milestones
| Measure |
Part I: Sequence AB
Participants received a single subcutaneous (SC) injection of 100 microgram (mcg) rhPTH(1-84) (Treatment A) on Day 1 of treatment period 1 followed by 100 mcg rhPTH (1-84) (Treatment B) on Day 1 of treatment period 2. A washout period of 96 hours was maintained between treatment periods 1 and 2.
|
Part I: Sequence BA
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of treatment period 1 followed by 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of treatment period 2. A washout period of 96 hours was maintained between treatment periods 1 and 2.
|
Part II: Sequence CDEF
Participants received a single SC injection of 25 mcg (Treatment C) rhPTH(1-84) on Day 1 of treatment period 1 followed by 50 mcg (Treatment D) rhPTH(1-84) on Day 1 of treatment period 2 followed by 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of treatment period 3 followed by 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
Part II: Sequence DFCE
Participants received a single SC injection of 50 mcg (Treatment D) rhPTH(1-84) on Day 1 of treatment period 1 followed by 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of treatment period 2 followed by 25 mcg (Treatment C) rhPTH(1-84) on Day 1 of treatment period 3 followed by 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
Part II: Sequence ECFD
Participants received a single SC injection of 75 mcg rhPTH(1-84) (Treatment E) on Day 1 of treatment period 1 followed by 25 mcg rhPTH(1-84) (Treatment C) on Day 1 of treatment period 2 followed by 200 mcg rhPTH(1-84) (Treatment F) on Day 1 of treatment period 3 followed by 50 mcg rhPTH(1-84) (Treatment D) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
Part II: Sequence FEDC
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of treatment period 1 followed by 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of treatment period 2 followed by 50 mcg (Treatment D) rhPTH(1-84) on Day 1 of treatment period 3 followed by 25 mcg (Treatment C) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
|---|---|---|---|---|---|---|
|
Part I: Treatment Period 1 (1 Day)
STARTED
|
42
|
42
|
0
|
0
|
0
|
0
|
|
Part I: Treatment Period 1 (1 Day)
COMPLETED
|
42
|
42
|
0
|
0
|
0
|
0
|
|
Part I: Treatment Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part I: Washout Period 1 (96 Hours)
STARTED
|
42
|
42
|
0
|
0
|
0
|
0
|
|
Part I: Washout Period 1 (96 Hours)
COMPLETED
|
42
|
42
|
0
|
0
|
0
|
0
|
|
Part I: Washout Period 1 (96 Hours)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part I: Treatment Period 2 (1 Day)
STARTED
|
42
|
42
|
0
|
0
|
0
|
0
|
|
Part I: Treatment Period 2 (1 Day)
COMPLETED
|
42
|
42
|
0
|
0
|
0
|
0
|
|
Part I: Treatment Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II: Treatment Period 1 (1 Day)
STARTED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 1 (1 Day)
COMPLETED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II: Washout Period 1 (48 Hours)
STARTED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Washout Period 1 (48 Hours)
COMPLETED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Washout Period 1 (48 Hours)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II: Treatment Period 2 (1 Day)
STARTED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 2 (1 Day)
COMPLETED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II: Washout Period 2 (48 Hours)
STARTED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Washout Period 2 (48 Hours)
COMPLETED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Washout Period 2 (48 Hours)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II: Treatment Period 3 (1 Day)
STARTED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 3 (1 Day)
COMPLETED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 3 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II: Washout Period 3 (48 Hours)
STARTED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Washout Period 3 (48 Hours)
COMPLETED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Washout Period 3 (48 Hours)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part II: Treatment Period 4 (1 Day)
STARTED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 4 (1 Day)
COMPLETED
|
0
|
0
|
3
|
3
|
3
|
3
|
|
Part II: Treatment Period 4 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Relative Bioavailability of a New Formulation Compared With the Approved Formulation of rhPTH [1-84] and to Find Out Dose Linearity of the New Formulation in Healthy Adults
Baseline characteristics by cohort
| Measure |
Part I: Sequence AB
n=42 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of treatment period 1 followed by 100 mcg rhPTH (1-84) (Treatment B) on Day 1 of treatment period 2. A washout period of 96 hours was maintained between treatment periods 1 and 2.
|
Part I: Sequence BA
n=42 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of treatment period 1 followed by 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of treatment period 2. A washout period of 96 hours was maintained between treatment periods 1 and 2.
|
Part II: Sequence CDEF
n=3 Participants
Participants received a single SC injection of 25 mcg (Treatment C) rhPTH(1-84) on Day 1 of treatment period 1 followed by 50 mcg (Treatment D) rhPTH(1-84) on Day 1 of treatment period 2 followed by 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of treatment period 3 followed by 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
Part II: Sequence DFCE
n=3 Participants
Participants received a single SC injection of 50 mcg (Treatment D) rhPTH(1-84) on Day 1 of treatment period 1 followed by 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of treatment period 2 followed by 25 mcg (Treatment C) rhPTH(1-84) on Day 1 of treatment period 3 followed by 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
Part II: Sequence ECFD
n=3 Participants
Participants received a single SC injection of 75 mcg rhPTH(1-84) (Treatment E) on Day 1 of treatment period 1 followed by 25 mcg rhPTH(1-84) (Treatment C) on Day 1 of treatment period 2 followed by 200 mcg rhPTH(1-84) (Treatment F) on Day 1 of treatment period 3 followed by 50 mcg rhPTH(1-84) (Treatment D) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
Part II: Sequence FEDC
n=3 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of treatment period 1 followed by 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of treatment period 2 followed by 50 mcg (Treatment D) rhPTH(1-84) on Day 1 of treatment period 3 followed by 25 mcg (Treatment C) rhPTH(1-84) on Day 1 of treatment period 4. A washout period of 48 hours was maintained between each treatment periods 1, 2, 3 and 4.
|
Total
n=96 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
41.5 years
STANDARD_DEVIATION 10.37 • n=5 Participants
|
45.3 years
STANDARD_DEVIATION 12.24 • n=7 Participants
|
36.7 years
STANDARD_DEVIATION 8.14 • n=5 Participants
|
38.0 years
STANDARD_DEVIATION 4.36 • n=4 Participants
|
45.7 years
STANDARD_DEVIATION 5.51 • n=21 Participants
|
40.0 years
STANDARD_DEVIATION 6.24 • n=10 Participants
|
43.0 years
STANDARD_DEVIATION 10.97 • n=115 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
56 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
40 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
35 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
74 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
22 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
83 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dosePopulation: Pharmacokinetic (PK) Set included all participants who had at least one measurable predose (baseline) and one postdose concentration of parathyroid hormone (PTH). Data was collected and analyzed as per individual treatment.
AUClast was a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration.
Outcome measures
| Measure |
Part I: Treatment A
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part I: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)
|
471.9 picogram*hour/milliliter (pg*hr/ml)
Geometric Coefficient of Variation 57.4
|
603.1 picogram*hour/milliliter (pg*hr/ml)
Geometric Coefficient of Variation 50.3
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dosePopulation: Pharmacokinetic (PK) Set included all participants who had at least one measurable predose (baseline) and one postdose concentration of parathyroid hormone (PTH). Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. Data was collected and analyzed as per individual treatment.
AUClast was a measure of the total amount of drug in the plasma from time zero to time of the last measurable concentration.
Outcome measures
| Measure |
Part I: Treatment A
n=11 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=12 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part II: Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of rhPTH (1-84)
|
44.34 pg*hr/ml
Geometric Coefficient of Variation 161.7
|
97.74 pg*hr/ml
Geometric Coefficient of Variation 123.4
|
259.2 pg*hr/ml
Geometric Coefficient of Variation 57.5
|
1009 pg*hr/ml
Geometric Coefficient of Variation 61.3
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dosePopulation: PK Set included all participants who had at least one measurable predose (baseline) and one postdose concentration of parathyroid hormone (PTH). Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. Data was collected and analyzed as per individual treatment.
AUCinf was the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration. AUC was be used as a measure of drug exposure. It was derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Outcome measures
| Measure |
Part I: Treatment A
n=73 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=79 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part I: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)
|
559.7 pg*hr/ml
Geometric Coefficient of Variation 53.2
|
663.7 pg*hr/ml
Geometric Coefficient of Variation 44.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dosePopulation: PK Set included all participants who had at least one measurable predose (baseline) and one postdose concentration of parathyroid hormone (PTH). Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. Data was collected and analyzed as per individual treatment.
AUCinf was the area under the curve extrapolated to infinity, calculated using the observed value of the last non-zero concentration. AUC was be used as a measure of drug exposure. It was derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Outcome measures
| Measure |
Part I: Treatment A
n=2 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=6 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
n=7 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=11 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part II: Area Under the Plasma Concentration- Time Curve From Time Zero to Infinity (AUCinf) of rhPTH(1-84)
|
83.91 pg*hr/ml
Geometric Coefficient of Variation 19.5
|
217.0 pg*hr/ml
Geometric Coefficient of Variation 33.2
|
364.7 pg*hr/ml
Geometric Coefficient of Variation 39.0
|
1117 pg*hr/ml
Geometric Coefficient of Variation 59.6
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dosePopulation: PK Set included all participants who had at least one measurable predose (baseline) and one postdose concentration of parathyroid hormone (PTH). Data was collected and analyzed as per individual treatment.
Cmax referred to the maximum (or peak) concentration that a drug achieved in the body after the drug had been administrated.
Outcome measures
| Measure |
Part I: Treatment A
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part I: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)
|
150.8 picogram per milliliter (pg/ml)
Geometric Coefficient of Variation 53.2
|
185.1 picogram per milliliter (pg/ml)
Geometric Coefficient of Variation 52.7
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, 0.08, 0.16, 0.33, 0.5, 0.75, 1.0, 1.25,1.5,2.0, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours post dosePopulation: PK Set included all participants who had at least one measurable predose (baseline) and one postdose concentration of parathyroid hormone (PTH). Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. Data was collected and analyzed as per individual treatment.
Cmax referred to the maximum (or peak) concentration that a drug achieved in the body after the drug had been administrated.
Outcome measures
| Measure |
Part I: Treatment A
n=11 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=12 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part II: Maximum Observed Plasma Concentration (Cmax) of rhPTH(1-84)
|
28.05 pg/ml
Geometric Coefficient of Variation 50.4
|
43.06 pg/ml
Geometric Coefficient of Variation 47.5
|
77.46 pg/ml
Geometric Coefficient of Variation 55.8
|
250.2 pg/ml
Geometric Coefficient of Variation 41.5
|
—
|
—
|
PRIMARY outcome
Timeframe: From start of study drug administration up to Day 34Population: Safety set included all participants who received at least one dose of the study drug. Data was collected and analyzed as per individual treatment.
Vital sign assessments included systolic and diastolic blood pressure, pulse rate and body temperature. Any change in vital signs which are deemed clinically significant by the investigator were reported.
Outcome measures
| Measure |
Part I: Treatment A
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Number of Participants With Clinically Significant Changes in Vital Signs Values
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of study drug administration up to Day 34Population: Safety set included all participants who received at least one dose of the study drug. Data was collected and analyzed as per individual treatment.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. A TEAE was an adverse event with a start date on or after the first dose of Investigational product (IP), or a start date before the date of the first dose of IP but increased in severity on or after the date of the first dose of IP. Number of participants with TEAEs was reported.
Outcome measures
| Measure |
Part I: Treatment A
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part I and II: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
|
19 Participants
|
15 Participants
|
2 Participants
|
4 Participants
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From start of study drug administration up to Day 34Population: Safety set included all participants who received at least one dose of the study drug. Data was collected and analyzed as per individual treatment.
Any change in ECG assessments which were deemed clinically significant by the investigator were reported.
Outcome measures
| Measure |
Part I: Treatment A
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part I and II: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters Reported as TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of study drug administration up to Day 34Population: Safety set included all participants who received at least one dose of the study drug. Data was collected and analyzed as per individual treatment.
Clinical laboratory tests included hematology, chemistry, and urinalysis. Any changes in clinical laboratory results which are deemed clinically significant by the investigator were reported.
Outcome measures
| Measure |
Part I: Treatment A
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=84 Participants
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
n=12 Participants
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 Participants
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Part I and II: Number of Participants With Clinically Significant Changes in Clinical Laboratory Values
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Part I: Treatment A
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Part I: Treatment B
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Part II: Treatment C
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Part II: Treatment D
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part II: Treatment E
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part II: Treatment F
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Part I: Treatment A
n=84 participants at risk
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment A) on Day 1 of one of the two treatment periods.
|
Part I: Treatment B
n=84 participants at risk
Participants received a single SC injection of 100 mcg rhPTH(1-84) (Treatment B) on Day 1 of one of the two treatment periods.
|
Part II: Treatment C
n=12 participants at risk
Participants received a single SC injection of 25 mcg (Treatment C) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment D
n=12 participants at risk
Participants received a single SC injection of 50 mcg (Treatment D) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment E
n=12 participants at risk
Participants received a single SC injection of 75 mcg (Treatment E) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
Part II: Treatment F
n=12 participants at risk
Participants received a single SC injection of 200 mcg (Treatment F) rhPTH(1-84) on Day 1 of one of the four treatment periods.
|
|---|---|---|---|---|---|---|
|
Investigations
Amylase increased
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.2%
1/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
General disorders
Asthenia
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Nervous system disorders
Dizziness
|
1.2%
1/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
1.2%
1/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
16.7%
2/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Nervous system disorders
Headache
|
8.3%
7/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
4.8%
4/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Investigations
Lipase increased
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Gastrointestinal disorders
Nausea
|
2.4%
2/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
6.0%
5/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
16.7%
2/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Vascular disorders
Pallor
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Gastrointestinal disorders
Toothache
|
1.2%
1/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Nervous system disorders
Tremor
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
General disorders
Vessel puncture site bruise
|
1.2%
1/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
1.2%
1/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
1.2%
1/84 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
8.3%
1/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
0.00%
0/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
16.7%
2/12 • From start of study drug administration up to Day 34
Safety set included all participants who received at least one dose of the study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER