A Drug Interaction Study of Folic Acid and Oral Contraceptive Tablets Containing Norgestimate (NGM)/Ethinyl Estradiol (EE) in Healthy Women.
Condition: Drug Interactions; Contraception; 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 oral contraceptive (OC) [250 mcg NGM/35 mcg EE] tablets.
    

Detailed description: 
      This is an open-label, randomized (study drug assigned by chance), single-center,
      pharmacokinetic interaction study. Healthy adult women who met the prestudy eligibility
      criteria were randomized to 1 of 2 treatment groups. The randomization was balanced using
      permuted blocks. Healthy volunteers in Group 1 were to receive a single oral dose of 250 µg
      NGM/35 mcg EE (1 tablet) on Days 1 and 17, and 1 mg of folic acid on Days 4 through 18.
      Healthy volunteers in Group 2 were to receive a single, oral 1 mg dose of folic acid on Days
      1 and 17, and 1 tablet on Days 2 through 17. Serial blood samples were to be collected from
      each healthy volunteer on Days 1 and 17 before dosing and at specified times for up to 72
      hours after dosing for pharmacokinetic evaluation. Healthy volunteers were to be confined
      overnight at the study unit on Days -1 and 16 for an overnight fast of at least 8 hours
      before dosing on Days 1 and 17. Healthy volunteers were to remain confined at the study unit
      until the 24-hour blood samples were collected on Days 2 and 18. Safety was based on the
      incidence of adverse events, and on changes in clinical laboratory values, vital signs,
      electrocardiograms, and physical and gynecological examination findings. The Sponsor
      prematurely terminated this study on 14 February 2005 because of errors made at the study
      site in healthy volunteer randomization, the timing of blood draws, and handling of
      laboratory samples. As a result of these errors, the pharmacokinetic samples collected were
      not analyzed, and a new study was initiated (NRGMON-CON-1006). Due to the premature
      termination of the study, no healthy volunteer received more than 9 days of therapy. Most
      healthy volunteers completed the screening and premature termination procedures.

      Oral contraceptives tablet (250 mcg NGM/35 mcg EE); Folic acid tablet (1 mg). Group 1: Single
      OC tablet on Days 1 and 17, 1 folic acid tablet on Days 4 to 18. Group 2: Single folic acid
      tablet on Days 1 and 17, 1 OC tablet on Days 2 to 17. The study drugs were to be taken with
      240 mL (8 oz) of water at approximately 8:00 a.m. Healthy volunteers were required to fast
      for a minimum of 8 hours before dosing on Days 1 and 17.
    

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; Folic Acid; Ortho-Cyclen; Female contraception; Ethinyl Estradiol; Drug Interactions; Pharmacokinetics; Contraceptives, Oral