A Phase I Study to Assess the Pharmacokinetics of GSK2798745 Tablets

NCT ID: NCT02925546

Last Updated: 2017-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2016-12-31

Brief Summary

GSK2798745 is being developed as a novel therapeutic intervention for the treatment of pulmonary edema associated with heart failure (HF) and is currently under investigation in the form of a compounded capsule. This is an open-label, randomized, single-dose, crossover study with the purpose to determine the pharmacokinetics (PK) of three 2.4 milligrams (mg) tablet formulations of GSK2798745 in 12 healthy subjects. The three formulations developed for this study will be micronized GSK2798745 active pharmaceutical ingredient (API) (Tablet A), micronized GSK2798745 API with sodium lauryl sulfate (SLS) and hypromellose (Tablet B), milled GSK2798745 API with SLS and hypermellose (Tablet C), and Tablet D, which will be either A/B/C based on interim PK analysis of data from the first three treatment periods.

Following a 30-day screening period, subjects will be randomized to one of the 6 treatment sequences: Treatment sequence 1: ABCD, 2=CABD, 3=ACBD, 4=BACD, 5=BCAD, 6=CBAD over three 4-day treatment periods. For treatment period 4, the best formulation based on the interim analysis data from the three treatment periods will be evaluated under fed conditions. Each treatment period will be separated by a minimum of 7 (+14)-day washout period. The total duration of participation in the study will be approximately 11 weeks including the follow-up visit.

Conditions

Heart Failure, Congestive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GSK2798745 ABCD treatment sequence

Subjects will be given 2.4 mg single oral doses of GSK2798745 (micronized API without SLS and hypromellose) in fasted state (treatment A), 2.4 mg of GSK2798745 (micronized API with SLS and hypromellose) in fasted state (treatment B), GSK2798745 (milled API with SLS and hypromellose) in fasted state (treatment C), and GSK2798745 tablet in fed state (treatment D) in either treatment periods 1, 2, or 3; the three treatment periods will each be separated by a minimum washout period of 7 days

Group Type: EXPERIMENTAL

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API; to be administered orally with 240 mL of water under fasted/fed conditions

GSK2798745 Micronized API with SLS and hypermellose (Tablet B)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions with 240 mL of water

GSK2798745 milled API without SLS and hypermellose (Tablet C)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of milled GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions, with 240 mL of water

GSK2798745 CABD treatment sequence

Subjects will be given 2.4 mg GSK2798745 (milled API with SLS and hypromellose) in fasted state (treatment C), 2.4 mg single oral doses of GSK2798745 (micronized API without SLS and hypromellose) in fasted state (treatment A), 2.4 mg of GSK2798745 (micronized API with SLS and hypromellose) in fasted state (treatment B), and GSK2798745 tablet in fed state (treatment D) in either treatment periods 1, 2, or 3; the three treatment periods will each be separated by a minimum washout period of 7 days

Group Type: EXPERIMENTAL

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API; to be administered orally with 240 mL of water under fasted/fed conditions

GSK2798745 Micronized API with SLS and hypermellose (Tablet B)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions with 240 mL of water

GSK2798745 milled API without SLS and hypermellose (Tablet C)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of milled GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions, with 240 mL of water

GSK2798745 ACBD treatment sequence

Subjects will be given 2.4 mg single oral doses of GSK2798745 (micronized API without SLS and hypromellose) in fasted state (treatment A), 2.4 mg GSK2798745 (milled API with SLS and hypromellose) in fasted state (treatment C), 2.4 mg of GSK2798745 (micronized API with SLS and hypromellose) in fasted state (treatment B), and GSK2798745 tablet in fed state (treatment D) in either treatment periods 1, 2, or 3; the three treatment periods will each be separated by a minimum washout period of 7 days

Group Type: EXPERIMENTAL

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API; to be administered orally with 240 mL of water under fasted/fed conditions

GSK2798745 Micronized API with SLS and hypermellose (Tablet B)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions with 240 mL of water

GSK2798745 milled API without SLS and hypermellose (Tablet C)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of milled GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions, with 240 mL of water

GSK2798745 BACD treatment sequence

Subjects will be given 2.4 mg of GSK2798745 (micronized API with SLS and hypromellose) in fasted state (treatment B), 2.4 mg of GSK2798745 (micronized API without SLS and hypromellose) in fasted state (treatment A), 2.4 mg GSK2798745 (milled API with SLS and hypromellose) in fasted state (treatment C), and GSK2798745 tablet in fed state (treatment D) in either treatment periods 1, 2, or 3; the three treatment periods will each be separated by a minimum washout period of 7 days

Group Type: EXPERIMENTAL

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API; to be administered orally with 240 mL of water under fasted/fed conditions

GSK2798745 Micronized API with SLS and hypermellose (Tablet B)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions with 240 mL of water

GSK2798745 milled API without SLS and hypermellose (Tablet C)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of milled GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions, with 240 mL of water

GSK2798745 BCAD treatment sequence

Subjects will be given 2.4 mg of GSK2798745 (micronized API with SLS and hypromellose) in fasted state (treatment B), 2.4 mg GSK2798745 (milled API with SLS and hypromellose) in fasted state (treatment C), 2.4 mg single oral doses of GSK2798745 (micronized API without SLS and hypromellose) in fasted state (treatment A), and GSK2798745 tablet in fed state (treatment D) in either treatment periods 1, 2, or 3; the three treatment periods will each be separated by a minimum washout period of 7 days

Group Type: EXPERIMENTAL

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API; to be administered orally with 240 mL of water under fasted/fed conditions

GSK2798745 Micronized API with SLS and hypermellose (Tablet B)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions with 240 mL of water

GSK2798745 milled API without SLS and hypermellose (Tablet C)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of milled GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions, with 240 mL of water

GSK2798745 CBAD treatment sequence

Subjects will be given 2.4 mg GSK2798745 (milled API with SLS and hypromellose) in fasted state (treatment C), 2.4 mg of GSK2798745 (micronized API with SLS and hypromellose) in fasted state (treatment B), 2.4 mg single oral doses of GSK2798745 (micronized API without SLS and hypromellose) in fasted state (treatment A), and GSK2798745 tablet in fed state (treatment D) in either treatment periods 1, 2, or 3; the three treatment periods will each be separated by a minimum washout period of 7 days

Group Type: EXPERIMENTAL

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API; to be administered orally with 240 mL of water under fasted/fed conditions

GSK2798745 Micronized API with SLS and hypermellose (Tablet B)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions with 240 mL of water

GSK2798745 milled API without SLS and hypermellose (Tablet C)

Intervention Type: DRUG

This is an immediate release tablet containing 2.4 mg of milled GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions, with 240 mL of water

Interventions

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API; to be administered orally with 240 mL of water under fasted/fed conditions

Intervention Type: DRUG

GSK2798745 Micronized API with SLS and hypermellose (Tablet B)

This is an immediate release tablet containing 2.4 mg of micronized GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions with 240 mL of water

Intervention Type: DRUG

GSK2798745 milled API without SLS and hypermellose (Tablet C)

This is an immediate release tablet containing 2.4 mg of milled GSK2798745 API with SLS and hypermellose; to be administered orally in fasted/fed conditions, with 240 mL of water

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Between 18 and 75 years of age inclusive, at the time of signing the informed consent

Exclusion Criteria

• Body weight >=50 kg and body mass index within the range 18 - 32 kilogram (kg)/meter (m)^2 (inclusive)
• Male or female of non-child bearing potential:

A male subject with a female partner of child bearing potential is eligible to participate if he agrees to use contraception as mentioned in the protocol during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period A female subject is eligible to participate if she is not a woman of childbearing potential (WOCBP) as defined in the protocol.

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol

• History of acute coronary syndromes including unstable angina or myocardial infarction within 6 months of screening
• History of stroke or seizure disorder within 5 years of Screening
• Active ulcer disease or gastrointestinal bleeding at the time of screening
• Alanine transaminase (ALT) and bilirubin >1.5x Upper limit of normal (ULN) is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• QT interval corrected according to Fridericia's formula (QTcF) >450 milliseconds (msec)
• History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the Medical Monitor, make the subject unsuitable for inclusion in this study
• Urinary cotinine levels indicative of current smoking or regular use of tobacco- or nicotine-containing products at time of screening (cotinine levels >200 nanogram [ng]/millimeter [mL])
• History of alcohol abuse within 6 months of the study based on the following criteria:

An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation
• Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at screening or within 3 months of screening.
• A positive test for human immunodeficiency virus antibody
• A positive pre-study drug/alcohol screen
• A screening cardiac Troponin level > ULN
• Use of another investigational product in a clinical study within the following time period prior to the first administration of study medication in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
• Exposure to more than 4 investigational medicinal products within 12 months prior to the first administration of study medication.
• Unable to refrain from the use of prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) except permitted medications listed in the protocol, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and/ or sponsor the medication will not interfere with the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Overland Park, Kansas, United States

Countries

United States

Other Identifiers

204725

Identifier Type: -

Identifier Source: org_study_id