A Pharmacokinetics (PK) and Safety Study to Determine the Effect of Repeat Dosing of Trametinib on Combined Oral Contraceptive (Norethindrone Plus Ethinyl Estradiol) in Female Subjects With Solid Tumors

Sponsor
GlaxoSmithKline
Study ID
NCT02292732
Phase
PHASE1
Status
Withdrawn

Conditions

  • Cancer

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 58 Years
Healthy Volunteers
Not accepted

Interventions

  • Trametinib 0.5 mg — DRUG
    Each tablet will contain GSK1120212B equivalent to 0.5 mg of Trametinib. Tablets are yellow, oval, biconvex, film-coated (4.85 x 8.86 millimeter \[mm\]) to be taken orally and once daily
  • Trametinib 2 mg — DRUG
    Each tablet will contain GSK1120212B equivalent to 2 mg Trametinib. Tablets are pink, round, biconvex and film-coated tablets (7.5 mm in diameter) to be taken orally and once daily.
  • ORTHO-NOVUM® tablet 1/35 — DRUG
    Each peach tablet will contain 1 mg of NE and 0.035 mg of EE. Other inactive ingredients will include lactose, magnesium stearate and pregelatinized corn starch
  • Placebo — DRUG
    Each green tablet will contain only inert ingredients: D\&C yellow No. 10 Aluminum Lake, FD\&C Blue No. 2 Aluminum Lake, lactose, magnesium stearate, microcrystalline cellulose, and pregelatinized cornstarch. The tablets are to be taken orally and once daily

Study Details

This is a Phase I, open-label, non-randomized, sequential, two-period, repeat-dose study to evaluate the effect of trametinib 2 milligram (mg) once daily on the repeat-dose pharmacokinetic (PK) of an oral contraceptive (OC) containing norethindrone (NE) and ethinyl estradiol (EE) (ORTHO-NOVUM® tablets: 1 mg NE + 0.035 mg EE) in female subjects with solid tumors. The study will determine PK interaction between trametinib and the components of combination oral contraceptives that would compromise the effectiveness of the contraceptives. The study will also evaluate the repeat dose PK of trametinib and its metabolite M5 using a validated assay. The study will enroll approximately 24 subjects. Each subject will participate in the study for approximately up to 13 to 15 weeks which will consist of a 30 day screening period, followed by 2 treatment periods (Period 1: 28 days and Period 2: ranging from 12 days to up to 21 days), and a transition visit or post-treatment follow-up visit. In Period 1, subjects will take one active tablet from the ORTHO-NOVUM® tablet 1/35 dial-pack once daily at approximately the same time each day for 21 days (Days 1 through 21), followed by one inert (referred to as placebo) tablet once daily at approximately the same time each day for 7 days (Days 22 through 28). In addition, subjects will take trametinib 2 mg (1 tablet) once daily at approximately the same time each day for a total of 17 days (Days 12 through 28). In Period 2, subjects will take one active tablet from the ORTHO-NOVUM® tablet 1/35 dial-pack once daily at approximately the same time each day for 11 days (Days 1 through 11). In addition, subjects will continue taking trametinib 2 mg (1 tablet) once daily at approximately the same time each day for 11 days (Days 1 through 11). ORTHO-NOVUM® is a registered trademark of Ortho Pharmaceutical Corporation.

Key Dates

Start date
Feb 29, 2016
Status verified
Jan 2016
Primary completion
May 31, 2017
Completion
May 31, 2017

Study Design

Enrollment
0 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Trametinib/ ORTHO-NOVUM® tablet
    Subjects in treatment period 1will take one active tablet from the ORTHO-NOVUM® tablet 1/35 dial-pack once daily at approximately the same time each day for 21 days (Days 1 through 21), followed by one placebo tablet once daily at approximately the same time each day for 7 days (Days 22 through 28). In addition, subjects will take trametinib 2 mg (1 tablet) once daily at approximately the same time each day for a total of 17 days (Days 12 through 28). Subjects in treatment period 2 will take one active tablet from the ORTHO-NOVUM® tablet 1/35 dial-pack once daily at approximately the same time each day for 11 days (Days 1 through 11). In addition, subjects will take trametinib 2 mg (1 tablet) once daily at approximately the same time each day for 11 days (Days 1 through 11).

Primary Outcome Measure

Composite of steady state PK parameters of NE and EE [ Time Frame: Day 11 and Day 12 of both the treatment periods ]

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