Last updated: 11/03/2018 15:06:58
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
An Open Label Study to Examine the Effects of a High-Fat Meal and Particle Size on the Pharmacokinetics of Orally Administered GSK2118436 in Subjects with BRAF Mutation Positive Tumor
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: An Open-Label Study to Examine the Effects of a High-Fat Meal and Particle Size on the Pharmacokinetics of Orally Administered GSK2118436 in Subjects with BRAF Mutation-Positive Tumor
Trial description: The study is designed to evaluate the effects of a high fat meal on the pharmacokinetics of 150 mg of GSK2118436, as well as the effects of particle size on the relative bioavailability of GSK2118436.
Primary purpose:
Prevention
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Area under the plasma-concentration time curve (AUC) of GSK2118436
Timeframe: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose
Maximum plasma concentration (Cmax) of GSK2118436
Timeframe: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose
Time to Cmax (Tmax) of GSK2118436
Timeframe: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose
Secondary outcomes:
Terminal half-life (t1/2) of GSK2118436
Timeframe: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose
AUC, Cmax, Tmax and t1/2 of GSK2118436 metabolites (GSK2285403, GSK2167542 and GSK2298683) and ratio of metabolite to parent drug GSK2118436
Timeframe: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose
Number of subjects with adverse events as a measure of safety and tolerability
Timeframe: From date of first dose until transition to rollover protocol BRF114144 (approximately 12 days) or study follow up visit if subject does not transition to BRF114144 (approx 22 days)
Interventions:
Drug: Regimen A
Drug: Regimen B
Drug: Regimen C
Drug: Regimen D
Enrollment:
28
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Cancer
Product
dabrafenib
Collaborators
GSK
Study date(s)
October 2010 to May 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Male or female at least 18 years of age at the time of signing the informed consent form;
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy) within the last three weeks; chemotherapy regimens without delayed toxicity within the last two weeks; or use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436;
- Current use of a prohibited medication or requires any of these medications during the study;
Inclusion and exclusion criteria
Inclusion criteria:
- Male or female at least 18 years of age at the time of signing the informed consent form;
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
- Body weight >/= to 45 kg and a Body Mass Index (BMI) >/= to 19 kg/m2 and less than or equal to 35 kg/m2 (inclusive);
- Able to swallow and retain oral medication;
- BRAF mutation-positive tumor as determined via relevant genetic testing;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at the time of transition to this study. NOTE: Subjects with an ECOG performance status of
- Women of child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control. Additionally, women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment;
- Must have adequate organ function as defined by the following values:
- Absolute neutrophil count (ANC) >/= to 1.2 x 10^9/L
- Hemoglobin >/= to 9 g/dL
- Platelets >/= to 100 x 10^9/L
- Serum bilirubin
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
- Serum creatinine /= 60 mL/min
- Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) < /= to 1.3 x ULN
- Left ventricular ejection fraction (LVEF) >/= to institutional lower limit of normal by Echocardiogram
Exclusion criteria:
- Currently receiving cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy) within the last three weeks; chemotherapy regimens without delayed toxicity within the last two weeks; or use of an investigational anti-cancer drug within 28 days preceding the first dose of GSK2118436;
- Current use of a prohibited medication or requires any of these medications during the study;
- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from seven days prior to the first dose of study medication;
- Current use of therapeutic warfarin (note: low molecular weight heparin and prophylactic low-dose warfarin are permitted);
- History of sensitivity to heparin or heparin-induced thrombocytopenia;
- Any major surgery within the last four weeks;
- Unresolved toxicity greater than National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) [NCI, 2009] Grade 2 from previous anti-cancer therapy except alopecia;
- Presence of active gastrointestinal disease or other condition (e.g., small bowel or large bowel resection) that will 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 for permission to enroll the subject;
- A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of HBV clearance may be enrolled with permission of the GSK medical monitor);
- Presence of invasive malignancy other than one of the malignancies covered under Inclusion Criterion #5; patients with a history of malignancy that have been definitively treated can be enrolled with approval of the GSK medical monitor;
- Subjects with brain metastases are excluded if their brain metastases are either: Symptomatic Treated (surgery, radiation therapy) but not clinically and radiographically stable one month after local therapy, or Asymptomatic and untreated but > 1 cm in the longest dimension Patients with small (≤ 1 cm in the longest dimension), asymptomatic brain metastases that do not need immediate local therapy can be enrolled with the approval of the GSK medical monitor. Subjects on a stable dose of corticosteroids for more than one month, or those who have been off corticosteroids for at least two weeks can be enrolled with approval of the GSK medical monitor. Subjects must also be off of enzyme-inducing anticonvulsants for more than four weeks;
- Presence of rheumatoid arthritis;
- History of alcohol or drug abuse within six months prior to screening;
- Corrected QT (QTc) interval >/= to 480 msecs;
- History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks;
- Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; abnormal cardiac valve morphology documented by echocardiogram (subjects with minimal abnormalities [ie, mild regurgitation/stenosis] can be entered on study with approval from the GSK medical monitor); or history of known cardiac arrhythmias (except sinus arrhythmias) within the past 24 weeks;
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs, or excipients (note: to date there are no known drugs chemically related to GSK2118436 which are approved by the Food and Drug Administration);
- Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol;
- Subjects with known glucose 6 phosphate dehydrogenase (G6PD) deficiency;
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer);
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period;
- Pregnant females as determined by positive human chorionic gonadotrophin (hCG) test at screening or prior to dosing;
- Lactating females who are actively breast feeding;
- Subject is mentally or legally incapacitated;
Trial location(s)
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84112
Status
Study Complete
Location
GSK Investigational Site
Scottsdale, Arizona, United States, 85259
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
No longer a GSK study
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Results for study 113468 can be found on the GSK Clinical Study Register.
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