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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00983957
First received: September 23, 2009
Last updated: September 16, 2015
Last verified: September 2015
  Purpose
The purpose of this study is to assess the effect of BMS-790052 on the pharmacokinetics of Ortho Tri-Cyclen® in healthy female subjects.

Condition Intervention Phase
Chronic Hepatitis C
Drug: BMS-790052
Drug: Ortho Tri-Cyclen®
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) of Ethinyl Estradiol [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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.

  • Area Under the Concentration-Time Curve (AUC) in 1 Dosing Interval of Ethinyl Estradiol [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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 of Maximum Observed Plasma Concentration of Ethinyl Estradiol [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Plasma Concentration of Norelgestromin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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.

  • Area Under the Concentration-Time Curve in 1 Dosing Interval of Norelgestromin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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.

  • Time of Maximum Observed Plasma Concentration of Norelgestromin [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Maximum Observed Plasma Concentration of Norgestrel [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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.

  • Area Under the Concentration-Time Curve in 1 Dosing Interval of Norgestrel [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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 of Maximum Observed Plasma Concentration of Norgestrel [ Time Frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose on Days 49 and 77 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died [ 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 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Laboratory Test Abnormalities [ Time Frame: From start of treatment (Day 1) up to Day 78 or discharge ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Demonstrating a Clinically Meaningful Effect in Vital Signs [ Time Frame: Baseline, Day 28, Day 29, Day 67, Day 68, Day 78, Day of discharge ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Demonstrating a Clinically Meaningful Effect in ECG Parameters [ Time Frame: Screening, Day 1, Day 67, Day 77 ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 47
Study Start Date: October 2009
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMS-790052 plus Ortho Tri-Cyclen® Drug: BMS-790052
Tablets, Oral, 60 mg, once daily, 10 days
Drug: Ortho Tri-Cyclen®
Tablets, Oral, once daily, 78 days

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00983957

Locations
United States, Arizona
MDS Pharma Services (US), Inc
Tempe, Arizona, United States, 85283
United States, Texas
Covance Clinical Research Unit, Inc.
Austin, Texas, United States, 78752
Canada, Quebec
Local Institution
St. Laurent, Quebec, Canada, H4R2N6
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00983957     History of Changes
Other Study ID Numbers: AI444-020 
Study First Received: September 23, 2009
Results First Received: August 18, 2015
Last Updated: September 16, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Hepatitis
Liver Diseases
Digestive System Diseases
Contraceptives, Oral, Combined
Norgestimate, ethinyl estradiol drug combination
Moxifloxacin
Fluoroquinolones
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 27, 2016