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Trial record 17 of 729 for:    Area Under Curve AND Bioavailability

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

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ClinicalTrials.gov Identifier: NCT02940522
Recruitment Status : Completed
First Posted : October 21, 2016
Results First Posted : November 30, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
AMAG Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Comparing Bioavailability When Makena® is Administered in Healthy Post-menopausal Women
Intervention Drug: Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)
Enrollment 122
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Period Title: Overall Study
Started 59 61
Completed 57 59
Not Completed 2 2
Reason Not Completed
Lost to Follow-up             1             2
Withdrawal by Subject             1             0
Arm/Group Title Treatment A Treatment B Total
Hide Arm/Group Description

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Total of all reporting groups
Overall Number of Baseline Participants 59 61 120
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants 61 participants 120 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
47
  79.7%
53
  86.9%
100
  83.3%
>=65 years
12
  20.3%
8
  13.1%
20
  16.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 59 participants 61 participants 120 participants
59.7  (6.16) 57.0  (5.68) 58.4  (6.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants 61 participants 120 participants
Female
59
 100.0%
61
 100.0%
120
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 59 participants 61 participants 120 participants
59 61 120
1.Primary Outcome
Title Comparison of Areas Under the Curve (AUC) to the Last Time With a Concentration ≥ LLOQ [AUC0-t] and to Infinity [AUCinf]
Hide Description 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
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Overall Number of Participants Analyzed 45 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr x ng/mL
AUC(0-t) Number Analyzed 45 participants 45 participants
2,313
(23.5%)
2,098
(27.7%)
AUC(inf) Number Analyzed 39 participants 41 participants
2,469
(22.8%)
2,175
(27.8%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison of bioavailability
Other Statistical Analysis The PK parameters were compared between treatments using an analysis of variance statistical model with treatment as the fixed effect, using the natural logarithms of the data. As the objective was to assess whether comparable exposure could be obtained using the higher SQ dose, the data were not normalized for dose before the statistical analysis.
2.Primary Outcome
Title Comparison of the Maximum Plasma Concentration (Cmax)
Hide Description Comparison of the maximum plasma concentration (Cmax) for the Primary PK Population
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Overall Number of Participants Analyzed 45 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
7.88
(71.9%)
6.91
(62.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison of bioavailability data
Other Statistical Analysis The PK parameters were compared between treatments using an analysis of variance statistical model with treatment as the fixed effect, using the natural logarithms of the data. As the objective was to assess whether comparable exposure could be obtained using the higher SQ dose, the data were not normalized for dose before the statistical analysis.
3.Secondary Outcome
Title Comparison of Tmax
Hide Description Comparison of PK parameter Tmax for the Primary PK population
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Overall Number of Participants Analyzed 45 45
Geometric Mean (Full Range)
Unit of Measure: hr
48.1
(18 to 342)
49.7
(2 to 336)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison of bioavailability data
Other Statistical Analysis The PK parameters were compared between treatments using an analysis of variance statistical model with treatment as the fixed effect, using the natural logarithms of the data. As the objective was to assess whether comparable exposure could be obtained using the higher SQ dose, the data were not normalized for dose before the statistical analysis.
4.Secondary Outcome
Title Comparison of AUC (0-168)
Hide Description Comparison of PK Parameter AUC (0-168) for the Primary PK Population
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Overall Number of Participants Analyzed 45 45
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr x ng/mL
813
(41.5%)
790
(55.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison of bioavailability data
Other Statistical Analysis The PK parameters were compared between treatments using an analysis of variance statistical model with treatment as the fixed effect, using the natural logarithms of the data. As the objective was to assess whether comparable exposure could be obtained using the higher SQ dose, the data were not normalized for dose before the statistical analysis.
5.Secondary Outcome
Title Comparison of t1/2
Hide Description Comparison of PK parameter t1/2 for the Primary PK Population
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Overall Number of Participants Analyzed 39 41
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr
212
(29.1%)
185
(25.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison of bioavailability data
Other Statistical Analysis The PK parameters were compared between treatments using an analysis of variance statistical model with treatment as the fixed effect, using the natural logarithms of the data. As the objective was to assess whether comparable exposure could be obtained using the higher SQ dose, the data were not normalized for dose before the statistical analysis.
6.Secondary Outcome
Title Comparison of Elimination Rate Constant
Hide Description Comparison of the elimination rate constant for the Primary PK Population
Time Frame 9 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description:

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Overall Number of Participants Analyzed 39 41
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 1/hr
0.0033
(29.1%)
0.0038
(25.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A, Treatment B
Comments [Not Specified]
Type of Statistical Test Other
Comments Comparison of bioavailability data
Other Statistical Analysis The PK parameters were compared between treatments using an analysis of variance statistical model with treatment as the fixed effect, using the natural logarithms of the data. As the objective was to assess whether comparable exposure could be obtained using the higher SQ dose, the data were not normalized for dose before the statistical analysis.
Time Frame 9 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment A Treatment B
Hide Arm/Group Description

Subcutaneous (SQ) injection using an autoinjector

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

Intramuscular injection (IM) using syringe and needle

Makena® (Hydroxyprogesterone Caproate Injection, 250 mg/mL)

All-Cause Mortality
Treatment A Treatment B
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment A Treatment B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/59 (0.00%)      0/61 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment A Treatment B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/59 (54.24%)      23/61 (37.70%)    
Gastrointestinal disorders     
Diarrhoea  1  3/59 (5.08%)  3 1/61 (1.64%)  1
Nausea  1  1/59 (1.69%)  2 1/61 (1.64%)  1
Abdominal discomfort  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Vomiting  1  1/59 (1.69%)  1 0/61 (0.00%)  0
General disorders     
Injection site pain  1  22/59 (37.29%)  25 5/61 (8.20%)  6
Injection site bruising  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Injection site discoloration  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Injection site erythema  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Injection site inflammation  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Injection site paraesthesia  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Injection site pruritis  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Pyrexia  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Vessel puncture site reaction  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Infections and infestations     
Upper respiratory tract infection  1  1/59 (1.69%)  1 3/61 (4.92%)  3
Nasopharyngitis  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Tooth abscess  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Urinary tract infection  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Injury, poisoning and procedural complications     
Arthropod bite  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Laceration  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Ligament sprain  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Thermal burn  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Tooth fracture  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Investigations     
Gamma-glutamyltransferase increased  1  1/59 (1.69%)  1 0/61 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Nervous system disorders     
Headache  1  9/59 (15.25%)  9 10/61 (16.39%)  10
Dizziness  1  1/59 (1.69%)  1 1/61 (1.64%)  1
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Skin and subcutaneous tissue disorders     
Rash  1  0/59 (0.00%)  0 1/61 (1.64%)  1
Vascular disorders     
Hot flush  1  2/59 (3.39%)  2 1/61 (1.64%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: AMAG Pharmaceuticals, Inc.
Phone: 1-877-411-2510
EMail: amag@druginfo.com
Layout table for additonal information
Responsible Party: AMAG Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02940522     History of Changes
Other Study ID Numbers: AMAG-HPC-PK-010
First Submitted: October 17, 2016
First Posted: October 21, 2016
Results First Submitted: April 24, 2018
Results First Posted: November 30, 2018
Last Update Posted: November 30, 2018