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

Organon and Co158 enrolled

Overview

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").

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

158

Conditions

Healthy Postmenopausal Females

Interventions

Eligibility

Sex: FEMALEMin age: 45 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC)

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.

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)

Baseline Corrected Maximum Observed Serum Concentration of E2 (Cmax of E2)

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.

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)

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

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.

Time frame: 0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose)

Baseline Corrected Area Under the Concentration-time Curve From Time 0 to 72 Hours (AUC72) for E2

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.

Time frame: 0 hours to 72 hours

Secondary Outcomes

Tmax of NOMAC

Time frame: 0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose)

Tmax of E2

Time frame: 0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose)

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)

t1/2 of E2

Time frame: 0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose)

Clearance (Calculated for NOMAC Only)

Time frame: blood samples were collected for NOMAC evaluation up to 144 hours postdose

Volume of Distribution (Calculated for NOMAC Only)

Time frame: blood samples were collected for NOMAC evaluation up to 144 hours postdose