GSK1120212 Food-effect Study

NCT01371487 | Completed Phase 1

• 1 other identifier: 113709
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of the this study is to evaluate the effect of a high-fat, high calorie meal on the single dose PK of GSK1120212 in subjects with solid tumors.

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• evaluate the effect of a high-fat, high-calorie meal on the PK of a single dose of GSK1120212 administered to subjects

  • Area under the plasma concentration-time curve from time zero (pre-dose) to time t (AUC(0-t)), AUC(0-inf), Cmax, and tmax.

  Predose - 168 hours post dose period 1 and 2

Secondary Outcomes (1)

• assess the short-term safety and tolerability of single oral doses of 2.0 mg of GSK1120212 administered to subjects

  Day 1/periods 1 and 2, Day 8 period 2 and follow-up.

Study Arms (2)

Treatment A

EXPERIMENTAL

GSK1120212 Dose /Treatment 2.0 mg/Fasted

Drug: GSK1120212

Treatment B

EXPERIMENTAL

GSK1120212 Dose /Treatment 2.0 mg/high fat, high calorie meal

Drug: GSK1120212

Interventions

GSK1120212 DRUG

Oral/once-daily single doses on Day 1 of Periods 1 and 2

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female; 18 years of age or older at the time of consent
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Able to swallow and retain oral medication.
• Histologically or cytologically confirmed diagnosis of a solid tumor.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 3).
• Adequate baseline organ function defined in Table 5 Definitions for Adequate Baseline Organ Function Absolute neutrophil count greater than or equal to 1.2 × 109/L Hemoglobin greater than or equal to9 g/dL Platelets greater than or equal to 75 × 109/L Prothrombin time (PT), International normalization ratio (INR)a and Partial thromboplastin time (PTT) less than or equal to 1.5 times ULN Hepatic Total bilirubin less than or equal to 1.5 times ULN ALT less than or equal to 2.5 times ULN Renal Creatinine or less than or equal to 1.5 times ULN Calculated creatinine clearance or greater than or equal to 50 mL/min 24-hour urine creatinine clearance greater than or equal to 50 mL/min Cardiac LVEF greater than or equal to LLNc by ECHO or MUGA
• INR greater than 1.5 times ULN will be acceptable in case of subjects receiving therapeutic anticoagulants such as warfarin as long as INR is monitored during the study according to clinical practice.
• Calculated by the Cockcroft-Gault formula (see Appendix 2).
• If LLN is not defined for a given institution, then ejection fraction must be greater than or equal to 50%.
• Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment and agree to use effective contraception, as defined in Section 7.1.1, during the study and for 6 weeks following the last dose of study treatment.
• Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in Section 7.1.2 from the time of the first dose of study treatment until 16 weeks following the last dose of study treatment (based on the lifecycle of sperm).

You may not qualify if:

• Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within 3 weeks prior to randomization; chemotherapy regimens without delayed toxicity within 2 weeks prior to randomization; or use of an investigational anti-cancer drug within 4 weeks prior to randomization.
• Has unresolved Grade 2 or greater toxicity (based on NCI-CTCAE, version 4.0) \[NCI Common Terminology Criteria for Adverse Events, 2009\] from previous anti-cancer therapy except Grade 2 decreased hemoglobin levels or alopecia.
• Has pre-existing peripheral neuropathy of greater than or equal to Grade 2.
• Has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product, whichever is longer, prior to the first dose of study treatment in this study.
• Has participated in a study that resulted in or made a donation of blood or blood products in excess of 500 mL within 56 days of the first dose of study treatment.
• Has presence of active GI disease or other condition (e.g., gastrectomy, bariatric surgery, small or large bowel resection, or cholecystectomy should be excluded) that may interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the GSK Medical Monitor.
• Has any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator or GSK Medical Monitor.
• Has a history of interstitial lung disease or pneumonitis.
• Is currently using a prohibited medication(s) or requires the use of any of the prohibited medications during the study (see Section 8.2).
• NOTE: Use of anticoagulants such as warfarin is permitted; however, INR must be monitored in accordance with local institutional practice.
• Has a history or current evidence/risk of RVO or CSR:
• History of RVO or CSR, or predisposing factors to RVO or CSR (i.e., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension or diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
• Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
• Evidence of new optic disc cupping
• Intraocular pressure greater than 21 mmHg as measured by tonography

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Cox DS, Papadopoulos K, Fang L, Bauman J, LoRusso P, Tolcher A, Patnaik A, Pendry C, Orford K, Ouellet D. Evaluation of the effects of food on the single-dose pharmacokinetics of trametinib, a first-in-class MEK inhibitor, in patients with cancer. J Clin Pharmacol. 2013 Sep;53(9):946-54. doi: 10.1002/jcph.115. Epub 2013 Jul 25.

  PMID: 23893461 DERIVED

Related Links

• Results for study 113709 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Neoplasms

Interventions

trametinib

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 9, 2011
• First Posted: June 10, 2011
• Study Start: May 2, 2011
• Primary Completion: September 30, 2011
• Study Completion: September 30, 2011
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

US (3)