A Bioequivalence Study of Norgestimate /Ethinyl Estradiol (NGM/EE) Tablets Manufactured at 2 Different Facilities

Healthy Clinical Trial

Official title:

A Single-Dose, Open-Label, Randomized, 2-Way Crossover Pivotal Study to Assess the Bioequivalence of NGM/EE Tablets Manufactured at 2 Different Facilities

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02127593
• Other study ID #: CR104172
• Secondary ID: 10131CON10012014
• Status: Completed
• Phase: Phase 1
• First received: April 29, 2014
• Last updated: October 2, 2014
• Start date: June 2013
• Est. completion date: September 2014

Study information

• Verified date: October 2014
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: The Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to establish the bioequivalence of the hormones norgestimate, norelgestromin, and ethinyl estradiol in norgestimate/ethinyl estradiol (NGM/EE) tablets, formulated by wet process compared with the same hormones in NGM/EE tablets, formulated by dry process, in healthy women.

Description:

This is a Phase 1, single-dose, open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, "unblinded"), randomized (the study medication is assigned by chance), single-center and a 2-way crossover (method used to switch participants from one study group to another in a clinical trial) study in healthy women. The study consists of 3 parts: Screening phase, Treatment phase and end-of-study or withdrawal. Treatment periods will be separated by a wash out period of at least 10 days. The duration of participation in the study for an individual participant will be approximately 7 weeks. All participants will be randomly assigned in a 1:1 ratio to 1 of 2 possible treatment sequences and receive both of the following treatments: 1 oral tablet formulated by wet process or dry process, whereas each tablet contains norgestimate 250 microgram (mcg) and ethinyl estradiol 35 mcg. The primary endpoint of the study will be assessment of pharmacokinetic parameters. Participants' safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Participants must be either surgically sterile or of child-bearing potential and be practicing an effective non-hormonal method of birth control (for example, copper intrauterine device, double-barrier method, male partner sterilization) before entry and throughout the study

• If a woman of child-bearing potential, must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening; and a negative urine pregnancy test on Day -1 of the each treatment period

• Participants must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after the last dose

• Body mass index (BMI: weight [kilogram {kg}]/height^2 [meter {m}]^2) between 18.5 and 30 kg/m^2 (inclusive), and body weight not less than 50 kilogram (kg) or higher than 90 kg (198 pounds)

• Participant must be a non-smoker

Exclusion Criteria:

• Participants have a levonorgestrel implant (for example, Norplant) in place or removed within the 30 days before admission to the study site

• Contraindications to combined hormonal contraceptives

• Participants who received medroxyprogesterone injection (for example, Depo Provera) within 6 months of admission to the study

• Use of any other hormonal contraceptive within 30 days of admission to the study site

• Participants with abnormal papanicolaou (Pap) smear or CytoRich test

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Norgestimate /Ethinyl estradiol tablets (NGM/EE) (Wet Process)
Norgestimate /Ethinyl estradiol tablets (NGM/EE) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, formulated by wet process will be orally administered on Day 1 of Period 1 or Period 2.
• Norgestimate /Ethinyl estradiol tablets (NGM/EE) (Dry Process)
Norgestimate /Ethinyl estradiol tablets (NGM/EE) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, formulated by dry process will be orally administered on Day 1 of Period 1 or Period 2.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (C[max])	The C(max) is the maximum serum concentration which will be observed at the defined time points.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last])	The AUC (last) is the area under the plasma concentration-time curve from time zero time of the last quantifiable concentration C(last), and C(last) is the last observed quantifiable concentration.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])	The AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Secondary	Time to Reach the Maximum Plasma Concentration (T[max])	The T[max] is time to reach the observed maximum plasma concentration.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Secondary	Percentage of AUC(0-infinity)	Percentage of AUC(0-infinity) is calculated as (AUC[0-infinity] minus AUC[0-last] divided by AUC[0-infinity]) multiplied by 100.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Secondary	Elimination Half-life Period (t1/2)	Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda (z).	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Secondary	Terminal slope (Lambda [z])	Terminal slope is defined by first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Secondary	Coefficient of Determination (r^2)	The coefficient of determination is a goodness of fit statistic that gives the proportion of the variance of one variable that is predictable from the other variable.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No
Secondary	Adjusted Coefficient of Determination (r^2 adj.)	The coefficient of determination adjusted (r^2 adj.) for the number of points used in the estimation of lambda[z].	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48 and 72 hours after study drug administration on Day 1 of Period 1 and Period 2	No