Relative Bioavailibilty for Pediatric Powder for Suspension (PfOS) Formulation

Tracking Information
First Submitted Date ICMJE	July 19, 2012
First Posted Date ICMJE	July 23, 2012
Last Update Posted Date	November 13, 2017
Actual Study Start Date ICMJE	July 30, 2012
Actual Primary Completion Date	November 12, 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 19, 2012)	Evaluate the relative bioavailability of a PfOS formulation relative to the commercial GSK1120212 tablet formulation in adult subjects with solid tumors [ Time Frame: 168 hours X 2 ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01647659 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 19, 2012)	Safety and tolerability as determined by the number of patients with adverse events, serious adverse events, and changes in lab values and vital signs from baseline [ Time Frame: Day 1 of each dosing session and followup ]; Evaluate the palatability (bitterness, sweetness, overall taste and aroma) of the pediatric formulation of GSK1120212 [ Time Frame: Day 1 ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Relative Bioavailibilty for Pediatric Powder for Suspension (PfOS) Formulation
Official Title ICMJE	An Open-Label, Two-Period, Randomized, Crossover Study to Assess the Relative Bioavailability of GSK1120212 Tablet Formulation and the GSK1120212 Pediatric Oral Solution Formulation Following Single-Dose Administration to Adult Subjects With Solid Tumors
Brief Summary	The purpose of this open-label, randomized, 2-treatment, 2-period crossover study with incomplete washout is to evaluate the relative bioavailability of 2mg GSK1120212 pediatric oral solution formulation in comparison to 2mg GSK1120212 tablet formulation, to investigate the safety and tolerability of a single dose of the GSK1120212 pediatric oral solution formulation as compared to a single dose of the GSK1120212 tablet formulation, and to investigate the palatability of the GSK1120212 pediatric oral solution formulation. Subjects will be assigned to one of two possible treatment sequences according to the randomization code provided to the sites by GSK: a single dose of 2mg GSK1120212 pediatric oral solution formulation then a single dose of 2mg GSK1120212 tablet formulation, or a single dose of 2mg GSK1120212 tablet formulation, then a single dose of 2mg GSK1120212 pediatric oral solution formulation. Administration of GSK1120212 in either sequence will be followed by 7 days of serial blood sampling for pharmacokinetic analysis of plasma GSK1120212. Safety assessments, including assessment of adverse events, clinical laboratory values (hematology, clinical chemistry and urinalysis) and vital signs, will be made throughout the study. After completing the pharmacokinetic assessments for two periods, eligible subjects may transition to MEK114375, an open-label rollover study of GSK1120212.
Detailed Description	The purpose of this open-label, randomized, 2-treatment, 2-period crossover study with incomplete washout is to evaluate the relative bioavailability of 2mg GSK1120212 pediatric oral solution formulation in comparison to 2mg GSK1120212 tablet formulation, to investigate the safety and tolerability of a single dose of the GSK1120212 pediatric oral solution formulation as compared to a single dose of the GSK1120212 tablet formulation, and to investigate the palatability of the GSK1120212 pediatric oral solution formulation. Subjects will be assigned to one of two possible treatment sequences according to the randomization code provided to the sites by GSK: a single dose of 2mg GSK1120212 pediatric oral solution formulation then a single dose of 2mg GSK1120212 tablet formulation, or a single dose of 2mg GSK1120212 tablet formulation, then a single dose of 2mg GSK1120212 pediatric oral solution formulation. Administration of GSK1120212 in either sequence will be followed by 7 days of serial blood sampling for pharmacokinetic analysis of plasma GSK1120212. Safety assessments, including assessment of adverse events, clinical laboratory values (hematology, clinical chemistry and urinalysis) and vital signs, will be made throughout the study. After completing the pharmacokinetic assessments for two periods, eligible subjects may transition to MEK114375, an open-label rollover study of GSK1120212.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Other
Condition ICMJE	Cancer
Intervention ICMJE	Drug: Trametinib tablet 2 mg, orally, on Day 1 of the dosing period; Drug: Trametinib pediatric formulation 2 mg, orally, on Day 1 of the dosing period
Study Arms	Experimental: GSK1120212 tablet GSK1120212 tablet Intervention: Drug: Trametinib tablet; Experimental: GSK1120212 powder for oral solution GSK1120212 powder for oral solution Intervention: Drug: Trametinib pediatric formulation
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 8, 2017)	18
Original Estimated Enrollment ICMJE; (submitted: July 19, 2012)	24
Actual Study Completion Date	November 12, 2012
Actual Primary Completion Date	November 12, 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Male or female, 18 years of age or older, at the time of signing the informed 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 malignancy that is not responsive to standard therapies; or for which there is no approved or curative therapy; or for subjects which refuse standard therapy.; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Adequate baseline organ function, defined as: absolute neutrophil count >= 1.2X10^9/L; hemoglobin >=9g/dL; platelets >=75X10^9/L; prothrombin time (PT), international normalized ratio (INR) and partial thromboplastin time (PTT) <=1.5 X upper limit of normal (ULN); total bilirubin <=1.5 X ULN; alanine aminotransferase <=2.5 X ULN; creatinine <=1.5 X ULN OR calculated creatinine clearance or 24-hour urine creatinine clearance >= 50mL/min; left ventricular ejection fraction (LVEF) >= lower limit of normal (LLN); systolic blood pressure <140mm Hg; Women of child-bearing potential must have a negative serum pregnancy test within 14 days of first dose of investigational product administration and agree to use effective contraception, as defined in the protocol, during the study and for 6 weeks following the last dose of investigational product.; Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 16 weeks after the last dose of GSK1120212. Exclusion criteria; 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.; Unresolved Grade 2 or greater toxicity (based on NCI-CTCAE, version 4.0, 2009) from previous anti-cancer therapy except Grade 2 decreased haemoglobin levels or alopecia.; Pre-existing peripheral neuropathy >= Grade 2.; Has participated in a clinical trial and received 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 investigational product in this study.; Has participated in a clinical trial that resulted in or made a donation of blood or blood products in excess of 500mL within 56 days of the first dose of investigational product in this study.; Has presence of active GI disease or other condition (e.g., gastrectomy, bariatric surgery, small or large bowel resection, or cholecystectomy) that may interfere significantly with absorption of drugs.; 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 with the study procedures, in the opinion of the investigator or the GSK medical monitor.; History of interstitial lung disease or pneumonitis.; History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR), including history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease(s) such as hypertension, 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, evidence of new visual field defects, or intraocular pressure > 21mm Hg.; Has symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression; NOTE: Subjects previously treated for these conditions that have had stable central nervous system (CNS) disease (verified with consecutive imaging studies) for >3 months, are asymptomatic and are not currently taking corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior to Day 1 of the study are permitted. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs (EIAEDs).; QTcB or QTcF >=480msec.; Subject has a history or evidence of cardiovascular risk, including any of the following: history or evidence of current clinically significant uncontrolled arrhythmias. Exception: subjects with controlled atrial fibrillation for >30days prior to randomization are eligible OR history of acute coronary syndromes, including myocardial infarction and unstable angina, coronary angioplasty, or stenting, within 6months prior to randomization.; History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA).
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01647659
Other Study ID Numbers ICMJE	115892
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	GlaxoSmithKline
Study Sponsor ICMJE	GlaxoSmithKline
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account	GlaxoSmithKline
Verification Date	November 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP