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

Phase 1

Completed

• Conditions: Healthy Postmenopausal Females
• Interventions: Drug: Commercial NOMAC-E2; Drug: Phase 3 NOMAC-E2 "Batch A"; Drug: Phase 3 NOMAC-E2 "Batch B"

• Registration Number: NCT01345786
• Lead Sponsor: Organon and Co

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").

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Study First Submitted: 2011-04-29
• Study First Submitted QC: 2011-04-29
• Study First Posted: 2011-05-02
• Results First Submitted: 2011-07-28
• Results First Submitted QC: 2011-07-28
• Results First Posted: 2011-08-29
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-07
• Last Update Posted: 2022-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 158

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Commercial NOMAC-E2, Part 1	Commercial NOMAC-E2	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".
Phase 3 NOMAC-E2, Part 1	Phase 3 NOMAC-E2 "Batch A"	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".
Commercial NOMAC-E2, Part 2	Commercial NOMAC-E2	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".
Phase 3 NOMAC-E2, Part 2	Phase 3 NOMAC-E2 "Batch B"	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".

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration of NOMAC (Cmax of NOMAC)	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)	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)	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)	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	0 hours to time of the last measurable sample (blood samples were collected for NOMAC evaluation up to 144 hours postdose)	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	0 hours to 72 hours	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

Name	Time	Method
Tmax of E2	0 hours to tmax of E2 (blood samples were collected for E2 evaluation up to 96 hours postdose)
Tmax of NOMAC	0 hours to tmax of NOMAC (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
Terminal Phase Half Life (t1/2) of NOMAC	0 hours to t1/2 (blood samples were collected for NOMAC evaluation up to 144 hours postdose)
t1/2 of E2	0 hours to t1/2 (blood samples were collected for E2 evaluation up to 96 hours postdose)
Clearance (Calculated for NOMAC Only)	blood samples were collected for NOMAC evaluation up to 144 hours postdose
Volume of Distribution (Calculated for NOMAC Only)	blood samples were collected for NOMAC evaluation up to 144 hours postdose