A Drug Interaction Study of Folic Acid and Oral Contraceptive Tablets Containing Norgestimate (NGM) /Ethinyl Estradiol (EE) in Healthy Women.
Condition: Drug Interactions; Healthy; Pharmacokinetics
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to assess the effect of folic acid administration on the blood
      level and the breakdown products of OC study drug (250 mcg norgestimate[NGM]/35 mcg Ethinyl
      Estradiol [EE]) tablets. The effect of study drug tablet intake on the blood level of folic
      acid is also determined.
    

Detailed description: 
      This is a single-center, open-label, pharmacokinetic drug interaction study between folic
      acid (1 mg) and study drug (250 mcg NGM/35 mcg EE) in 2 groups of at least 20 healthy women
      each. In Group 1, a single oral dose of 250 mcg NGM/35 mcg EE study drug was administered to
      the healthy volunteers at the study site on Days 1 and 17 and folic acid 1 mg was
      administered orally on Days 4 to 18; in Group 2, folic acid 1 mg was administered orally on
      Days 1 and 17 at the study site and 1 tablet of study drug was administered on Days 2 to 17.
      Blood samples were collected at specified times for 72 hours postdose on Days 1 and 17 for
      the healthy volunteers in Group 1 for determination of blood levels of norelgestromin (NGMN),
      and norgestrel (NG) [the active breakdown product of NGM], and EE. For the healthy volunteers
      in Group 2, blood samples were collected for 24 hours after the folic acid dose on Days 1 and
      17 for determination of plasma levels of total folates. Safety was evaluated based on the
      following: the incidence, type and severity of adverse events; clinical laboratory tests;
      vital sign and electrocardiogram (ECGs) measurements; and physical examinations. Oral
      temperature, pulse, respiratory rate, and sitting blood pressure (BP) were taken before
      dosing on Days 1 and 17. For Group 1, measurements were taken before and at least 15 minutes
      after the 24-hour (Days 2 and 18), 48-hour (Days 3 and 19), and 72-hour (Day 4)
      pharmacokinetic blood draw; and at study completion (Day 20) or early withdrawal. For Group
      2, measurements were taken before and at least 15 minutes after the 24-hour pharmacokinetic
      blood draw on Days 2 and 18; and at study completion (Day 18) or early withdrawal. Physical
      and gynecologic examinations and 12-lead ECGs were performed at screening and at study
      completion or early withdrawal. Blood samples for blood chemistry, hematology, and urine
      samples for urinalysis were collected at the screening visit and at the follow-up visit or
      early withdrawal.

      Oral contraceptives tablet (250 mcg NGM/35 mcg EE); Folic acid tablet (1 mg). In Group 1, a
      single oral dose of (250 mcg NGM/35 mcg EE) study drug was administered on Days 1 and 17 and
      folic acid 1 mg was administered orally on Days 4 to 18; in Group 2, folic acid 1 mg was
      administered orally on Days 1 and 17 and 1 tablet of study drug was administered on Days 2 to
      17. Study drugs were taken with 240 mL (8 oz) of water at approximately 8:00 a.m.
    

Intervention name(s): Norgestimate; Ethinyl Estradiol; Folic acid
Intervention type(s): Drug
Intervention MeSH terms: Folic Acid; Ethinyl Estradiol; Norgestimate; Estradiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Norgestimate; Contraceptives, Oral; Ortho-Cyclen; Folic Acid; Ethinyl Estradiol