A Bioequivalence Study of Norgestimate /Ethinyl Estradiol (NGM/EE) Tablets Manufactured at 2 Different Facilities
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02127593
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 101
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description First NGM/EE (Dry Process), then NGM/EE (Wet Process) Norgestimate /Ethinyl estradiol tablets (NGM/EE) (Wet Process) Participants will receive 1 tablet (formulated by dry process) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, orally on Day 1 of Period 1, followed by 1 tablet (formulated by wet process) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, orally on Day 1 of Period 2, wherein Period 1 and Period 2 are separated by a wash out period of at least 10 days. First NGM/EE (Wet Process), then NGM/EE (Dry Process) Norgestimate /Ethinyl estradiol tablets (NGM/EE) (Dry Process) Participants will receive 1 tablet (formulated by wet process) containing norgestimate 250 microgram (mcg) and ethinyl estradiol 35 mcg, orally on Day 1 of Period 1, followed by 1 tablet (formulated by dry process) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, orally on Day 1 of Period 2, wherein Period 1 and Period 2 are separated by a wash out period of at least 10 days. First NGM/EE (Dry Process), then NGM/EE (Wet Process) Norgestimate /Ethinyl estradiol tablets (NGM/EE) (Dry Process) Participants will receive 1 tablet (formulated by dry process) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, orally on Day 1 of Period 1, followed by 1 tablet (formulated by wet process) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, orally on Day 1 of Period 2, wherein Period 1 and Period 2 are separated by a wash out period of at least 10 days. First NGM/EE (Wet Process), then NGM/EE (Dry Process) Norgestimate /Ethinyl estradiol tablets (NGM/EE) (Wet Process) Participants will receive 1 tablet (formulated by wet process) containing norgestimate 250 microgram (mcg) and ethinyl estradiol 35 mcg, orally on Day 1 of Period 1, followed by 1 tablet (formulated by dry process) containing norgestimate 250 mcg and ethinyl estradiol 35 mcg, orally on Day 1 of Period 2, wherein Period 1 and Period 2 are separated by a wash out period of at least 10 days.
- Primary Outcome Measures
Name Time Method Maximum Plasma Concentration (C[max]) 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 The C(max) is the maximum serum concentration which will be observed at the defined time points.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) 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 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.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) 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 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.
- Secondary Outcome Measures
Name Time Method Coefficient of Determination (r^2) 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 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.
Adjusted Coefficient of Determination (r^2 adj.) 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 The coefficient of determination adjusted (r\^2 adj.) for the number of points used in the estimation of lambda\[z\].
Time to Reach the Maximum Plasma Concentration (T[max]) 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 The T\[max\] is time to reach the observed maximum plasma concentration.
Percentage of AUC(0-infinity) 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 Percentage of AUC(0-infinity) is calculated as (AUC\[0-infinity\] minus AUC\[0-last\] divided by AUC\[0-infinity\]) multiplied by 100.
Elimination Half-life Period (t1/2) 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 Elimination half-life associated with the terminal slope (lambda\[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda (z).
Terminal slope (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 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.