Study to Investigate the Absorption, Distribution, Metabolism and Elimination of [14C]GSK1120212

Phase 1

Completed

• Conditions: Cancer
• Interventions: Drug: GSK1120212

• Registration Number: NCT01387204
• Lead Sponsor: GlaxoSmithKline

Brief Summary

GSK1120212 is a reversible and highly selective allosteric inhibitor of MEK1 and MEK2 activation and kinase activity currently being developed for the treatment of malignant melanoma. This is a Phase I, open-label, non-randomized, single-dose study designed to characterize the absorption, distribution, metabolism, and elimination (ADME) of a single oral dose of MEK inhibitor \[14C\]GSK1120212 as a solution in male subjects with solid tumor malignancies. A sufficient number of subjects will be enrolled to complete approximately four evaluable subjects. Following completion of the study, subjects may elect to continue dosing with GSK1120212 in the rollover study, MEK114375.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-15
• Study First Submitted: 2011-06-09
• Study First Submitted QC: 2011-06-30
• Study First Posted: 2011-07-04
• Primary Completion: 2011-07-18
• Study Completion: 2011-07-18
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-08
• Last Update Posted: 2017-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

Inclusion Criteria

1. Male 18 years old or older.
2. Written informed consent provided
3. Body weight greater than or equal to 45 kg and a BMI greater than or equal to 19 kg/m2 and less than or equal to 35 kg/m2 (inclusive).
4. Able to swallow and retain oral medication.
5. Histologically or cytologically confirmed diagnosis of a solid tumor.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
7. Agree to use one of the contraception methods listed in the protocol from the time of the first dose of study medication until sixteen weeks after the last dose of study medication.
8. A history of regular bowel movements (approximately once per day).
9. Adequate baseline organ function as listed in the protocol.

Exclusion Criteria

1. Currently receiving cancer therapy as specified in the protocol.

2. Serious and/or unstable pre-existing medical psychiatric disorder, or other conditions.

3. Any major surgery within the last four weeks.

4. Unresolved toxicity equal to or greater than Grade 2 from previous anti-cancer therapy except alopecia.

5. An occupation within the past 12 months which requires monitoring for radiation exposure, nuclear medicine procedures or excessive x-rays.

6. Radiation exposure from the previous three year period over 10 mSv if exposed to ionizing radiation above background as a result of work with radiation as category A (classified) workers or as a result of research studies.

7. History of interstitial lung disease or pneumonitis.

8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to dimethyl sulfoxide (DMSO).

9. Current use of a prohibited medications described in the protocol.

   • Use of anticoagulants such as warfarin is permitted.

10. History RVO or CSR.

    • Predisposing factors to RVO or CSR.

    • Visible retinal pathology that is considered a risk factor for RVO or CSR such as:

      • Evidence of new optic disc cupping

      • Intraocular pressure greater than 21 mm Hg as measured by tonography. 11.1. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. (Previously treated and have had stable CNS disease for greater than 3 months, asymptomatic and off corticosteroids, or on stable dose of corticosteroids for at least 1 month prior to study Day 1 are permitted).

11.2. Receiving enzyme inducing anti-epileptic drugs (EIAEDs). 12. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months. 13. QTcB greater than or equal to 480 msec. 14. History or evidence of current clinically significant uncontrolled arrhythmias.

15. History or evidence of current greater than or equal to Class II congestive heart failure.

16. Active gastrointestinal disease or other condition (e.g., gastrectomy, bariatric surgery, small bowel or large bowel resection, or cholecystectomy).

17. A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus, or Hepatitis C Virus.

18. Alcohol or drug abuse within six months prior to screening. 19. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs or excipients.

19. Participated in a clinical trial and has received an investigational product within 30 days or five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before the 1st dose.

20. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

21. Mentally or legally incapacitated.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single-Dose, 2 mg [14C]GSK1120212	GSK1120212	A single 2 mg (2 mg/10mL) oral dose of \[14C\]GSK1120212 containing approximately 79 μCi of radioactivity will be delivered as a solution.

Primary Outcome Measures

Name	Time	Method
Total excretion of radioactivity	11 days	• Total and relative excretion of radioactivity in urine and feces following a single, 2 mg oral solution dose of \[14C\]GSK1120212

Secondary Outcome Measures

Name	Time	Method
Total radioactivity concentration in blood and plasma	11 days	AUC(0- t), AUC(0-∞), Cmax, tmax and t1/2
Blood:plasma ratio	11 days	Blood:plasma ratio of total drug-related material (radioactivity)
Assess covalent binding of drug related material to plasma proteins	11 days	Assess percentage of drug-related material that covalently bonds to plasma proteins (studied separately under a DMPK protocol)
Pharmacokentic concentrations in plasma	11 days	Plasma GSK1120212 concentrations AUC(0-t), AUC(0-∞), Cmax, tmax, and t1/2
Characterize and quantify metabolites in urine plasma and feces	11 days	Characterize and quantify metabolites of GSK1120212 in plasma, urine and feces (studied separately under a DMPK protocol).
AEs	From dosing on Day 1 to Follow-up	Number of adverse events (AEs)
Vital signs	Screening, Day -1, Day 1, Day 5, and Follow-up	Changes from baseline
ECGs	Screening, Day 1 pre-dose, 24 hours, Day 11 and Follow-up	Changes from baseline
Clinical Laboratory assessments	Screening, Day -1, and Day 11	Changes from baslines

Trial Locations

Locations (1)

GSK Investigational Site; 🇺🇸 Tacoma, Washington, United States