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CancerPhase 1NCT01231568

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

A Phase 1 study testing Regimen A, Regimen B and Regimen C in people with Cancer, run by GlaxoSmithKline at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
What is being tested?
Regimen A, Regimen B and Regimen C
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
4 sitesUnited States
Study dates
21 Oct 2010to 13 May 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 </= to 2 may be eligible with the approval of the GlaxoSmithKline (GSK) Medical Monitor.
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  • 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 </= to 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= to 2.5 x ULN; <5 x ULN if liver metastases are present (with approval of GSK medical monitor)
  • Serum creatinine </= to ULN or calculated creatinine clearance >/= 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

Who cannot join

  • 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;
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  • 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 locations and contacts

4 sites in 1 country.

United States4 sites

  • GSK Investigational Site

    Detroit, Michigan, 48201

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    Salt Lake City, Utah, 84112

  • GSK Investigational Site

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

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

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.

Read the detailed description

GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that is currently being developed for the treatment of BRAF mutation-positive tumors. This study is designed to evaluate the effects of particle size on the relative bioavailability of GSK2118436 (Cohort 1) and to evaluate the effects of a high-fat meal on the pharmacokinetics of GSK2118436 (Cohort 2). Subjects will randomly receive two of four possible regimens over two periods. Subjects enrolled in Cohort 1 will receive a single 150 mg dose of GSK2118436 as micronized particles fasted (gelatin capsule formulation) and a single 150 mg dose of GSK2118436 as non-micronized particles fasted (larger particle size). Subjects enrolled in Cohort 2 will receive a single 150 mg dose of GSK2118436 (HydroxyPropyl Methyl Cellulose (HPMC) capsule formulation) fasted and with a high-fat breakfast. GSK2118436 will be administered as the mesylate salt (equivalent to 150 mg free base). Safety and tolerability will also be evaluated. The study will be conducted at a sufficient number of centers to complete approximately 28 adult subjects (14 subjects per cohort) with BRAF mutation-positive tumors. Following completion of this study, subjects may continue dosing with GSK2118436 in the roll-over study, Protocol BRF114144.

Conditions
Cancer
Being tested
Regimen A, Regimen B, Regimen C, Regimen D
Keywords
food effect; high fat meal, GSK2118436, pharmacokinetic, particle size, BRAF inhibitor, BRAF positive tumor
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Regimen ADrug

    Two gelatin capsules containing 75 mg GSK2118436A (dosed as the mesylate salt, micronized particles, equivalent to 150 mg free base), dosed fasted

  • Regimen BDrug

    Two gelatin capsules containing 75 mg GSK2118436A (dosed as the mesylate salt, larger, non-micronized particles, equivalent to 150 mg free base), dosed fasted

  • Regimen CDrug

    Two Hydroxy Propyl Methyl Cellulose (HPMC) capsules containing 75 mg GSK2118436A (dosed as the mesylate salt, micronized particles, equivalent to 150 mg free base), dosed fasted

  • Regimen DDrug

    Two HPMC capsules containing 75 mg GSK2118436A (dosed as the mesylate salt, micronized particles, equivalent to 150 mg free base), dosed with a high-fat meal

Study groups in NCT01231568
Study groupRoleWhat they receive
Cohort 1 Treatment Sequence 1ExperimentalSubjects will receive two 75 mg micronized gelatin capsules, dosed fasted (Regimen A) in Period 1 and two 75 mg non-micronized gelatin capsules, dosed fasted (Regimen B) in Period 2. Dosing will occur in the morning of Day 1 in each period, and dosing between periods will be separated by at least one week.
Receives: Drug: Regimen A; Drug: Regimen B
Cohort 1 Treatment Sequence 2ExperimentalSubjects will receive two 75 mg non-micronized gelatin capsules, dosed fasted (Regimen B) in Period 1 and two 75 mg micronized gelatin capsules, dosed fasted (Regimen A) in Period 2. Dosing will occur in the morning of Day 1 in each period, and dosing between periods will be separated by at least one week.
Receives: Drug: Regimen A; Drug: Regimen B
Cohort 2 Treatment Sequence 1ExperimentalSubjects will receive two 75 mg micronized HPMC capsules, dosed fasted (Regimen C) in Period 1 and two 75 mg micronized HPMC capsules, dosed with a high-fat meal (Regimen D) in Period 2. Dosing will occur in the morning of Day 1 in each period, and dosing between periods will be separated by at least one week.
Receives: Drug: Regimen C; Drug: Regimen D
Cohort 2 Treatment Sequence 2ExperimentalSubjects will receive two 75 mg micronized HPMC capsules, dosed with a high-fat meal (Regimen D) in Period 1 and two 75 mg micronized HPMC capsules, dosed fasted (Regimen C) in Period 2. Dosing will occur in the morning of Day 1 in each period, and dosing between periods will be separated by at least one week.
Receives: Drug: Regimen C; Drug: Regimen D

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area under the plasma-concentration time curve (AUC) of GSK2118436

    Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose

  2. Maximum plasma concentration (Cmax) of GSK2118436

    Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose

  3. Time to Cmax (Tmax) of GSK2118436

    Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose

Secondary outcomes (3)

  1. Terminal half-life (t1/2) of GSK2118436

    Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose

  2. AUC, Cmax, Tmax and t1/2 of GSK2118436 metabolites (GSK2285403, GSK2167542 and GSK2298683) and ratio of metabolite to parent drug GSK2118436

    Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose

  3. Number of subjects with adverse events as a measure of safety and tolerability

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2010 (estimated)
  2. Study start21 Oct 2010
  3. Primary completion13 May 2011
  4. Study completion13 May 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01231568
Sponsor's protocol ID
113468
Status last verified
Nov 2017
First submitted
21 Oct 2010
Last updated
14 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Ouellet D, Grossmann KF, Limentani G, Nebot N, Lan K, Knowles L, Gordon MS, Sharma S, Infante JR, Lorusso PM, Pande G, Krachey EC, Blackman SC, Carson SW. Effects of particle size, food, and capsule shell composition on the oral bioavailability of dabrafenib, a BRAF inhibitor, in patients with BRAF mutation-positive tumors. J Pharm Sci. 2013 Sep;102(9):3100-9. doi: 10.1002/jps.23519. Epub 2013 Apr 22.

    PubMed 23608920

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Regimen A, Regimen B and Regimen C in people with Cancer, run by GlaxoSmithKline at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under the plasma-concentration time curve (AUC) of GSK2118436 (time frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01231568, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2017.

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