Trial Outcomes & Findings for Comparing Bioavailability When Preservative-free Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) is Administered as an Intramuscular Manual Injection or as a Subcutaneous Injection Using an Auto-injector in Healthy Post-menopausal Women (NCT NCT02940522)
NCT ID: NCT02940522
Last Updated: 2022-04-28
Results Overview
Comparison of areas under the curve (AUC) to the last time with a concentration ≥ LLOQ \[AUC0-t\] and to infinity \[AUCinf\] for the Primary PK Population
COMPLETED
PHASE1
122 participants
9 weeks
2022-04-28
Participant Flow
Participant milestones
| Measure |
Treatment A
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Overall Study
STARTED
|
59
|
61
|
|
Overall Study
COMPLETED
|
57
|
59
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
Treatment A
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Comparing Bioavailability When Preservative-free Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL) is Administered as an Intramuscular Manual Injection or as a Subcutaneous Injection Using an Auto-injector in Healthy Post-menopausal Women
Baseline characteristics by cohort
| Measure |
Treatment A
n=59 Participants
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=61 Participants
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
47 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Age, Continuous
|
59.7 years
STANDARD_DEVIATION 6.16 • n=5 Participants
|
57.0 years
STANDARD_DEVIATION 5.68 • n=7 Participants
|
58.4 years
STANDARD_DEVIATION 6.05 • n=5 Participants
|
|
Sex: Female, Male
Female
|
59 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
59 participants
n=5 Participants
|
61 participants
n=7 Participants
|
120 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 9 weeksPopulation: The Primary PK Population consisted of 45 subjects each for both treatments for whom whole blood was analyzed. Subjects were excluded from Treatment A and Treatment B due to insufficient number of samples for planned analyses.
Comparison of areas under the curve (AUC) to the last time with a concentration ≥ LLOQ \[AUC0-t\] and to infinity \[AUCinf\] for the Primary PK Population
Outcome measures
| Measure |
Treatment A
n=45 Participants
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=45 Participants
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf]
AUC(0-t)
|
2,313 hr x ng/mL
Geometric Coefficient of Variation 23.5
|
2,098 hr x ng/mL
Geometric Coefficient of Variation 27.7
|
|
Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf]
AUC(inf)
|
2,469 hr x ng/mL
Geometric Coefficient of Variation 22.8
|
2,175 hr x ng/mL
Geometric Coefficient of Variation 27.8
|
PRIMARY outcome
Timeframe: 9 weeksPopulation: The Primary PK Population consisted of 45 subjects each for both treatments for whom whole blood was analyzed. Subjects were excluded from Treatment A and Treatment B due to insufficient number of samples for planned analyses.
Comparison of the maximum plasma concentration (Cmax) for the Primary PK Population
Outcome measures
| Measure |
Treatment A
n=45 Participants
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=45 Participants
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Comparison of the Maximum Plasma Concentration (Cmax)
|
7.88 ng/mL
Geometric Coefficient of Variation 71.9
|
6.91 ng/mL
Geometric Coefficient of Variation 62.9
|
SECONDARY outcome
Timeframe: 9 weeksPopulation: The Primary PK Population consisted of 45 subjects each for both treatments for whom whole blood was analyzed. Subjects were excluded from Treatment A and Treatment B due to insufficient number of samples for planned analyses.
Comparison of PK parameter Tmax for the Primary PK population
Outcome measures
| Measure |
Treatment A
n=45 Participants
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=45 Participants
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Comparison of Tmax
|
48.1 hr
Interval 18.0 to 342.0
|
49.7 hr
Interval 2.0 to 336.0
|
SECONDARY outcome
Timeframe: 9 weeksPopulation: The Primary PK Population consisted of 45 subjects each for both treatments for whom whole blood was analyzed. Subjects were excluded from Treatment A and Treatment B due to insufficient number of samples for planned analyses.
Comparison of PK Parameter AUC (0-168) for the Primary PK Population
Outcome measures
| Measure |
Treatment A
n=45 Participants
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=45 Participants
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Comparison of AUC (0-168)
|
813 hr x ng/mL
Geometric Coefficient of Variation 41.5
|
790 hr x ng/mL
Geometric Coefficient of Variation 55.5
|
SECONDARY outcome
Timeframe: 9 weeksPopulation: The Primary PK Population consisted of 45 subjects each for both treatments for whom whole blood was analyzed. Subjects were excluded from Treatment A and Treatment B due to insufficient number of samples for planned analyses.
Comparison of PK parameter t1/2 for the Primary PK Population
Outcome measures
| Measure |
Treatment A
n=39 Participants
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=41 Participants
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Comparison of t1/2
|
212 hr
Geometric Coefficient of Variation 29.1
|
185 hr
Geometric Coefficient of Variation 25.5
|
SECONDARY outcome
Timeframe: 9 weeksPopulation: The Primary PK Population consisted of 45 subjects each for both treatments for whom whole blood was analyzed. Subjects were excluded from Treatment A and Treatment B due to insufficient number of samples for planned analyses.
Comparison of the elimination rate constant for the Primary PK Population
Outcome measures
| Measure |
Treatment A
n=39 Participants
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=41 Participants
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
Comparison of Elimination Rate Constant
|
0.0033 1/hr
Geometric Coefficient of Variation 29.1
|
0.0038 1/hr
Geometric Coefficient of Variation 25.5
|
Adverse Events
Treatment A
Treatment B
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=59 participants at risk
Subcutaneous (SQ) injection using an autoinjector
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
Treatment B
n=61 participants at risk
Intramuscular injection (IM) using syringe and needle
Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
|
|---|---|---|
|
General disorders
Injection site pain
|
37.3%
22/59 • Number of events 25 • 9 weeks.
|
8.2%
5/61 • Number of events 6 • 9 weeks.
|
|
General disorders
Injection site bruising
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
General disorders
Injection site discoloration
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
General disorders
Injection site erythema
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
General disorders
Injection site inflammation
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
General disorders
Injection site paraesthesia
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
General disorders
Injection site pruritis
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
General disorders
Pyrexia
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
General disorders
Vessel puncture site reaction
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Nervous system disorders
Headache
|
15.3%
9/59 • Number of events 9 • 9 weeks.
|
16.4%
10/61 • Number of events 10 • 9 weeks.
|
|
Nervous system disorders
Dizziness
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Infections and infestations
Upper respiratory tract infection
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
4.9%
3/61 • Number of events 3 • 9 weeks.
|
|
Infections and infestations
Nasopharyngitis
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Infections and infestations
Tooth abscess
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Infections and infestations
Urinary tract infection
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.1%
3/59 • Number of events 3 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Gastrointestinal disorders
Nausea
|
1.7%
1/59 • Number of events 2 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Gastrointestinal disorders
Vomiting
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Injury, poisoning and procedural complications
Laceration
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Vascular disorders
Hot flush
|
3.4%
2/59 • Number of events 2 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Investigations
Gamma-glutamyltransferase increased
|
1.7%
1/59 • Number of events 1 • 9 weeks.
|
0.00%
0/61 • 9 weeks.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/59 • 9 weeks.
|
1.6%
1/61 • Number of events 1 • 9 weeks.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place