A Drug-Drug Interaction Study to Assess the Effect of Trametinib on the Pharmacokinetics of an Oral Contraceptive in Female Patients With Solid Tumors

NCT02705963 | Completed Phase 1 FDA Drug

• 1 other identifier: CTMT212X2102
• Study Type: interventional
• Target: 19
• Locations: 5 countries
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the effect of trametinib once daily on the pharmacokinetics (PK) of a daily dosing oral contraceptives (OCs) containing norethindrone (NE) and ethinyl estradiol (EE) in female patients with solid tumors. The PK of trametinib and its metabolite M5 will also be assessed.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics parameter: AUCtau of NE and EE alone and in combination with trametinib

  To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.

  Day 5 and 6 and 21 and 22

• Pharmacokinetics parameter: AUClast of NE and EE alone and in combination with trametinib

  To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.

  Day 5 and 6 and 21 and 22

• Pharmacokinetics parameter: Cmax of NE and EE alone and in combination with trametinib

  To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.

  Day 5 and 6 and 21 and 22

• Pharmacokinetics parameter: Tmax of NE and EE alone and incombination with trametinib

  To evaluate the effect of multiple doses of trametinib (2 mg once daily) on the steady state pharmacokinetics of combination OC (NE and EE) in female patients with solid tumors.

  Days 5 and 6 and 21 and 22

Secondary Outcomes (4)

• Pharmacokinetics parameter: AUClast of M5

  Day 21 and 22

• Pharmacokinetics parameter: AUCtau of M5

  Day 21 and 22

• Pharmacokinetics parameter: Cmax of M5

  Day 21 and 22

• Pharmacokinetics parameter: Tmax of M5

  Day 21 and 22

Study Arms (1)

Oral Contraceptive / Trametinib

EXPERIMENTAL

In treatment period 1 of the PK Phase patients will take the Oral Contraceptive once daily from Days 1-5. Period 2 of the PK Phase starts on Day 6 when patients take both the Oral Contraceptive and trametinib once daily from Days 6 to 21. Patients may continue dosing with trametinib only once daily from Day 22 onwards (post PK Phase).

Drug: Trametinib; Drug: Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol)

Interventions

Trametinib DRUG

Each tablet is 2mg trametinib to be taken orally once daily.

Oral Contraceptive / Trametinib

Oral Contraceptive (1mg norethindrone, 0.035mg ethinyl estradiol) DRUG

Combined oral contraceptive to be taken orally once daily.

Oral Contraceptive / Trametinib

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may not qualify if:

• Meets one of the following criteria: Is currently on a stable regimen of an oral contraceptive containing 1mg NE and 0.035mg EE, or Is willing to switch to a regimen of an oral contraceptive containing 1mg NE and 0.035mg EE from a stable regimen of an alternate OC, or Is willing to start a regimen of an oral contraceptive containing 1mg NE and 0.035mg EE.
• Meets one of the following criteria: Is post-menopausal, or, Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during dosing and for four months after stopping medication.
• Has no prior treatment-related toxicities \>Grade 1 (except alopecia) at the time of enrolment.
• Patient must meet the following laboratory values at the screening visit: Absolute Neutrophil Count ≥1.5 x 109/L. Platelets ≥75 x 109/L. Hemoglobin (Hgb) ≥9 g/dL. Serum creatinine \<1.5 mg/dL. Total bilirubin ≤1.5 x upper limit of normal (ULN) (isolated bilirubin \>1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). Aspartate transaminase (AST) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ≤5.0 x ULN. Alanine transaminase (ALT) ≤ 3.0 x ULN, except for patients with liver metastasis or tumor infiltration, who may only be included if ALT ≤5.0 x ULN. Prothrombin time (PT)/International normalized ratio (INR) and Partial thromboplastin time (PTT) ≤1.5xULN. Note: patients receiving therapeutic anticoagulation agents prior screening are permitted. Albumin 2.5 g/dL.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease
• Has had any major surgery, extensive radiotherapy, or anti-cancer therapy (e.g., chemotherapy with delayed toxicity, biologic therapy, or immunotherapy) within 21 days prior to enrolment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrolment. Prolonged immobilization must have resolved prior to enrolment.
• Has a known or suspected carcinoma that is excluded as administration of Oral Contraceptive would be contraindicated.
• Has a history of another malignancy.
• Has a history of interstitial lung disease or pneumonitis.
• Has a history of RVO.
• Has a history of any of conditions that would contraindicate administration of an OC
• Has symptomatic or untreated leptomeningeal, brain metastases, or spinal cord compression.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Karmanos Cancer Institute Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Novartis Investigative Site

Edegem, 2650, Belgium

Location

Novartis Investigative Site

Namur, 5000, Belgium

Location

Novartis Investigative Site

Maastricht, 6229 HX, Netherlands

Location

Novartis Investigative Site

Málaga, 29010, Spain

Location

Novartis Investigative Site

London, W1G 6AD, United Kingdom

Location

Related Links

• Results for CTMT212X2102 can be found on the Novartis Clinical Trial Results Website
• A Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Interventions

trametinib; Contraceptives, Oral; Norethindrone; Ethinyl Estradiol

Intervention Hierarchy (Ancestors)

Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norpregnatrienes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: March 11, 2016
• Study Start: October 20, 2016
• Primary Completion: August 29, 2019
• Study Completion: August 29, 2019
• Last Updated: February 9, 2022

Record last verified: 2021-10

Locations

BE (2); NL (1); US (2); GB (1); ES (1)