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

Bristol-Myers Squibb47 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Masking

NONE

Enrollment

Conditions

Chronic Hepatitis C

Interventions

BMS-790052DRUG

Tablets, Oral, 60 mg, once daily, 10 days

Ortho Tri-Cyclen®DRUG

Tablets, Oral, once daily, 78 days

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (3)

MDS Pharma Services (US), Inc

Tempe, Arizona, United States

Covance Clinical Research Unit, Inc.

Austin, Texas, United States

Local Institution

Saint-Laurent, Quebec, Canada

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: Screening, Day 1, Day 67, Day 77