Clinical trial NCT01345786: Bioequivalence of Nomegestrol Acetate (NOMAC) and Estradiol (E2) in Commercial Versus Phase 3 Pivotal Clinical Batches of NOMAC-E2 Tablets (P06328)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Postmenopausal Females
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2011-05-02
Enrollment: 158
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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").


Eligibility 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC)
timeFrame: 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)
measure: Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2)
timeFrame: 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)
measure: 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
timeFrame: 0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
measure: Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2
timeFrame: 0 hours to 72 hours
Secondary outcomes:
measure: Tmax of NOMAC
timeFrame: 0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
measure: Tmax of E2
timeFrame: 0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose)
measure: Terminal Phase Half Life (t1/2) of NOMAC
timeFrame: 0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
measure: t1/2 of E2
timeFrame: 0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose)
measure: Clearance (Calculated for NOMAC Only)
timeFrame: blood samples were collected for NOMAC evaluation up to 144 hours postdose
measure: Volume of Distribution (Calculated for NOMAC Only)
timeFrame: blood samples were collected for NOMAC evaluation up to 144 hours postdose
Other outcomes:
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