Bioequivalence of Nomegestrol Acetate (NOMAC) and Estradiol (E2) in Commercial Versus Phase 3 Pivotal Clinical Batches of NOMAC-E2 Tablets (COMPLETED) (P06328)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01345786
First received: April 29, 2011
Last updated: February 13, 2014
Last verified: February 2014
  Purpose

For the contraceptive application a film-coated tablet has been developed which combines nomegestrol acetate (NOMAC) with estradiol (E2). This was an open-label, randomized, single-dose, four-way, replicate, cross-over study design conducted in 2 parallel parts at two sites, one site per study part. The primary objective of Part 1 was to assess the bioequivalence of NOMAC and E2 of the drug product manufactured using the commercial process ("commercial batch") versus the Phase 3 drug product ("Batch A"). The primary objective of Part 2 was to assess bioequivalence of NOMAC and E2 of the drug product manufactured using the commercial process ("commercial batch") versus the Phase 3 drug product ("Batch B").


Condition Intervention Phase
Healthy Postmenopausal Females
Drug: Commercial NOMAC-E2
Drug: Phase 3 NOMAC-E2 "Batch A"
Drug: Phase 3 NOMAC-E2 "Batch B"
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A 2-part, Cross-over Trial of NOMAC-E2 to Assess Bioequivalence Between the Phase 3 Pivotal Clinical Batches and a Batch Prepared Using the Commercial Drug Manufacturing Process

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC) [ Time Frame: 0 hours to time of maximum observed plasma concentration of NOMAC (tmax of NOMAC) (blood samples were collected for NOMAC evaluation up to 144 hours postdose) ] [ Designated as safety issue: No ]

    Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2.

    Blood samples for pharmacokinetic (PK) evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.


  • Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2) [ Time Frame: 0 hours to time of maximum observed serum concentration of E2 (tmax of E2) (blood samples were collected for E2 evaluation up to 96 hours postdose) ] [ Designated as safety issue: No ]

    Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2.

    Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.


  • Area Under the Concentration-time Curve From Time 0 to the Time of the Last Measurable Sample (AUC Last) and Area Under the Concentration-time Curve From Time 0 to Infinity (AUC Infinity) for NOMAC [ Time Frame: 0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose) ] [ Designated as safety issue: No ]

    Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2.

    AUClast is the AUC from time 0 to the time of the final quantifiable sample.

    AUC infinity is the AUC from time 0 to infinity.

    Blood samples for PK evaluation of NOMAC were collected at predose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 144 hours postdose Day 1.


  • Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2 [ Time Frame: 0 hours to 72 hours ] [ Designated as safety issue: No ]

    Bioequivalence for NOMAC and E2 were tested on the primary PK parameters: Cmax, AUC(infinity), and AUClast for NOMAC; and baseline adjusted AUC72 and Cmax for E2.

    AUC72 is the AUC from time 0 to 72 hours.

    Blood samples for PK evaluation of E2 were collected predose (-1, -0.5, and 0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose Day 1; multiple predose samples were needed to correct for endogenous levels.



Secondary Outcome Measures:
  • Tmax of NOMAC [ Time Frame: 0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose) ] [ Designated as safety issue: No ]
  • Tmax of E2 [ Time Frame: 0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose) ] [ Designated as safety issue: No ]
  • Terminal Phase Half Life (t1/2) of NOMAC [ Time Frame: 0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose) ] [ Designated as safety issue: No ]
  • t1/2 of E2 [ Time Frame: 0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose) ] [ Designated as safety issue: No ]
  • Clearance (Calculated for NOMAC Only) [ Time Frame: blood samples were collected for NOMAC evaluation up to 144 hours postdose ] [ Designated as safety issue: No ]
  • Volume of Distribution (Calculated for NOMAC Only) [ Time Frame: blood samples were collected for NOMAC evaluation up to 144 hours postdose ] [ Designated as safety issue: No ]

Enrollment: 158
Study Start Date: November 2009
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Commercial NOMAC-E2, Part 1
Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".
Drug: Commercial NOMAC-E2
1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination commercial tablet orally in the morning on Day 1 for all periods
Other Name: SCH 900121
Active Comparator: Phase 3 NOMAC-E2, Part 1
Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch A"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 1 were from "Site 1".
Drug: Phase 3 NOMAC-E2 "Batch A"
1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination tablet from the Phase 3 clinical trial program ("Batch A") orally in the morning on Day 1 for all periods
Other Name: SCH900121
Experimental: Commercial NOMAC-E2, Part 2
Participants received a single oral dose of the NOMAC-E2 fixed-dose combination commercial tablet (2.5 mg NOMAC/1.5 mg E2), either on the first day of Period 1 and Period 3 (for participants randomized to Sequence 1) or on the first day of Period 2 and Period 4 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Drug: Commercial NOMAC-E2
1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination commercial tablet orally in the morning on Day 1 for all periods
Other Name: SCH 900121
Active Comparator: Phase 3 NOMAC-E2, Part 2
Participants received a single oral dose of the NOMAC-E2 fixed-dose combination tablet (2.5 mg NOMAC/1.5 mg E2) from the Phase 3 clinical trial program ("Batch B"), either on the first day of Period 2 and Period 4 (for participants randomized to Sequence 1) or on the first day of Period 1 and Period 3 (for participants randomized to Sequence 2). Participants in Part 2 were from "Site 2".
Drug: Phase 3 NOMAC-E2 "Batch B"
1 x 2.5 mg NOMAC/1.5 mg E2 fixed dose combination tablet from the Phase 3 clinical trial program ("Batch B") orally in the morning on Day 1 for all periods
Other Name: SCH 900121

  Eligibility

Ages Eligible for Study:   45 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Key Inclusion Criteria:

  • Healthy postmenopausal females between the ages of 45 and 70 years, inclusive, having a Body Mass Index (BMI) between 18 and 32, inclusive;
  • Free of any clinically significant disease that would interfere with the study evaluations.

Key Exclusion Criteria:

  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug;
  • History of any infectious disease that affected the subject's ability to participate in the trial;
  • History of alcohol or drug abuse in the past 2 years;
  • Previously received NOMAC-E2;
  • Current participation in another clinical study or had participated in a clinical study (eg, laboratory or clinical evaluation) within 30 days of baseline;
  • Smoked more than 10 cigarettes or equivalent tobacco use per day;
  • History of malignancy;
  • Contraindications for the use of contraceptive steroids;
  • Recent history of medication use of certain medications specified in the protocol.
  Contacts and Locations
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  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01345786     History of Changes
Other Study ID Numbers: P06328
Study First Received: April 29, 2011
Results First Received: July 28, 2011
Last Updated: February 13, 2014
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on July 24, 2014