Study to Assess the Effect of BMS-790052 on the Pharmacokinetics of Ortho Tri-Cyclen® in Healthy Female Subjects

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of BMS-790052 on the pharmacokinetics of Ortho Tri-Cyclen® in healthy female subjects.

Official Title
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The Effect of the Co-administration of BMS-790052 on the Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinyl Estradiol and Norgestimate (Ortho Tri-Cyclen®) in Healthy Female Subjects

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: BMS-790052
* Drug: Ortho Tri-Cyclen®


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy female subjects, 18-45 years, BMI 18-32 kg/m². Must be using an adequate method of contraception to avoid pregnancy throughout the study. Key Exclusion Criteria: Abnormal Pap smear within 1 yr of dosing, and abnormal menstrual cycle during the 3 months prior to enrollment. Any significant or chronic uncontrolled medical illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-790052 plus Ortho Tri-Cyclen®<br> | Drug: BMS-790052<br>* Tablets, Oral, 60 mg, once daily, 10 days<br>Drug: Ortho Tri-Cyclen®<br>* Tablets, Oral, once daily, 78 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol | Ethinyl Estradiol is an analyte of Ortho Tri-Cyclen. Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) by a validated analytical method during the period of known analyte stability. Cmax was measured in picograms per milliliter (pg/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Days 49 and 77 | 
| Area Under the Concentration-Time Curve (AUC) in 1 Dosing Interval of Ethinyl Estradiol | Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in picograms multiplied by hours (h) per milliliter (pg*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 
| Time of Maximum Observed Plasma Concentration of Ethinyl Estradiol | Ethinyl Estradiol was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 
| Maximum Observed Plasma Concentration of Norelgestromin | Norelgestromin is a major active metabolite of norgestimate (NGM) which is found in Ortho Tri-Cyclen. Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Cmax was measured in nanograms per milliliter (ng/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 
| Area Under the Concentration-Time Curve in 1 Dosing Interval of Norelgestromin | Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in nanograms multiplied by hours (h) per milliliter (ng*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 
| Time of Maximum Observed Plasma Concentration of Norelgestromin | Norelgestromin was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration of Norgestrel | Norgestrel is an NGM metabolite and was measured in plasma using liquid chromatography-mass spectrometry by a validated analytical method during the period of known analyte stability. Cmax was measured in picograms per milliliter (pg/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 
| Area Under the Concentration-Time Curve in 1 Dosing Interval of Norgestrel | Norgestrel was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. AUC(TAU) was measured in picograms multiplied by hours (h) per milliliter (pg*h/mL) and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 
| Time of Maximum Observed Plasma Concentration of Norgestrel | Norgestrel was measured in plasma, using liquid chromatography-tandem mass spectrometry by a validated analytical method during the period of known analyte stability. Tmax was measured in hours (h), and derived from 24 hour plasma concentration versus time data using non-compartmental methods. Pre-dose concentrations and concentrations prior to the first quantifiable concentration that were below the lower limit of quantitation were treated as missing. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 | 
| Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. | For AEs from start of treatment (Day 1) up to Day 78 or discharge and for SAEs from Day 1 to 30 days after last dose of study drug | 
| Number of Participants With Laboratory Test Abnormalities | Laboratory marked abnormalities were defined as Hematocrit (low) as <0.85*Pre-treatment (PreRx), Hemoglobin (low) as <0.85*PreRx, Aspartate Aminotransferase (AST) (high) as >1.25*PreRx if PreRx > upper limits of normal (ULN); >1.25*ULN if PreRx <=ULN; >1.25*ULN if PreRx = Missing, Blood in urine (high) as ≥2 PreRx if PreRx ≥1; ≥2 if PreRx <1; ≥2 if PreRx = Missing. | From start of treatment (Day 1) up to Day 78 or discharge | 
| Number of Participants Demonstrating a Clinically Meaningful Effect in Vital Signs | Vital Signs were measured after the participant was seated quietly for at least 5 minutes and included systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature. Baseline = Last non-missing pretreatment value. | Baseline, Day 28, Day 29, Day 67, Day 68, Day 78, Day of discharge | 
| Number of Participants Demonstrating a Clinically Meaningful Effect in ECG Parameters | The electrocardiogram (ECG) evaluations were performed within ± 15 minutes of the relative time points. ECGs were recorded after the participants were in supine position for at least 5 minutes. ECG parameters measured were: PR interval, QRS complex, QT interval and corrected QT (QTc). | Screening, Day 1, Day 67, Day 77 |