NCT02925546

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2016

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2016

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

October 4, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 6, 2016

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

January 25, 2017

Status Verified

January 1, 2017

Enrollment Period

2 months

First QC Date

October 4, 2016

Last Update Submit

January 24, 2017

Conditions

Heart Failure, Congestive

Keywords

HealthyPharmacokineticsPhase IGSK2798745Tablet

Outcome Measures

Primary Outcomes (2)

  • Area under the curve (AUC) of GSK2798745

    AUC will be determined following a single oral dose of GSK2798745 under fasted conditions (Treatment periods 1-3) and fed conditions (Treatment period 4)

    Blood samples will be collected at the following time points: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 15 (Day 1), 24 and 36 (Day 2), 48 (Day 3) and 72 hours (Day 4) post dose in each of the treatment periods

  • Maximum plasma concentration (Cmax) of GSK2798745

    Cmax will be determined following a single oral dose of GSK2798745 under fasted conditions (Treatment periods 1-3) and fed conditions (Treatment period 4)

    Blood samples will be collected at the following time points: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 15 (Day 1), 24 and 36 (Day 2), 48 (Day 3) and 72 hours (Day 4) post dose in each of the treatment periods

Secondary Outcomes (16)

  • Time to maximum observed concentration (Tmax) of GSK2798745

    Blood samples will be collected at the following time points: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 15 (Day 1), 24 and 36 (Day 2), 48 (Day 3) and 72 hours (Day 4) post dose in each of the treatment periods

  • Elimination half-life (T1/2) of GSK2798745

    Blood samples will be collected at the following time points: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 15 (Day 1), 24 and 36 (Day 2), 48 (Day 3) and 72 hours (Day 4) post dose in each of the treatment periods

  • AUC of GSK2798745 following a standard Food Drug Administration (FDA) high fat, high calorie meal

    Blood samples will be collected at the following time points: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 15 (Day 1), 24 and 36 (Day 2), 48 (Day 3) and 72 hours (Day 4) post dose in treatment period 4

  • Cmax of GSK2798745 following a standard FDA high fat, high calorie meal

    Blood samples will be collected at the following time points: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 15 (Day 1), 24 and 36 (Day 2), 48 (Day 3) and 72 hours (Day 4) post dose in treatment period 4

  • Systolic and diastolic blood pressure as a measure of safety and tolerability of GSK2798745

    Up to 11 weeks

  • +11 more secondary outcomes

Study Arms (6)

GSK2798745 ABCD treatment sequence

EXPERIMENTAL

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

Drug: GSK2798745 Micronized API without SLS and hypermellose (Tablet A)Drug: GSK2798745 Micronized API with SLS and hypermellose (Tablet B)Drug: GSK2798745 milled API without SLS and hypermellose (Tablet C)

GSK2798745 CABD treatment sequence

EXPERIMENTAL

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

Drug: GSK2798745 Micronized API without SLS and hypermellose (Tablet A)Drug: GSK2798745 Micronized API with SLS and hypermellose (Tablet B)Drug: GSK2798745 milled API without SLS and hypermellose (Tablet C)

GSK2798745 ACBD treatment sequence

EXPERIMENTAL

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

Drug: GSK2798745 Micronized API without SLS and hypermellose (Tablet A)Drug: GSK2798745 Micronized API with SLS and hypermellose (Tablet B)Drug: GSK2798745 milled API without SLS and hypermellose (Tablet C)

GSK2798745 BACD treatment sequence

EXPERIMENTAL

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

Drug: GSK2798745 Micronized API without SLS and hypermellose (Tablet A)Drug: GSK2798745 Micronized API with SLS and hypermellose (Tablet B)Drug: GSK2798745 milled API without SLS and hypermellose (Tablet C)

GSK2798745 BCAD treatment sequence

EXPERIMENTAL

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

Drug: GSK2798745 Micronized API without SLS and hypermellose (Tablet A)Drug: GSK2798745 Micronized API with SLS and hypermellose (Tablet B)Drug: GSK2798745 milled API without SLS and hypermellose (Tablet C)

GSK2798745 CBAD treatment sequence

EXPERIMENTAL

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

Drug: GSK2798745 Micronized API without SLS and hypermellose (Tablet A)Drug: GSK2798745 Micronized API with SLS and hypermellose (Tablet B)Drug: GSK2798745 milled API without SLS and hypermellose (Tablet C)

Interventions

GSK2798745 Micronized API without SLS and hypermellose (Tablet A)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 ABCD treatment sequenceGSK2798745 ACBD treatment sequenceGSK2798745 BACD treatment sequenceGSK2798745 BCAD treatment sequenceGSK2798745 CABD treatment sequenceGSK2798745 CBAD treatment sequence
GSK2798745 Micronized API with SLS and hypermellose (Tablet B)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 ABCD treatment sequenceGSK2798745 ACBD treatment sequenceGSK2798745 BACD treatment sequenceGSK2798745 BCAD treatment sequenceGSK2798745 CABD treatment sequenceGSK2798745 CBAD treatment sequence
GSK2798745 milled API without SLS and hypermellose (Tablet C)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 ABCD treatment sequenceGSK2798745 ACBD treatment sequenceGSK2798745 BACD treatment sequenceGSK2798745 BCAD treatment sequenceGSK2798745 CABD treatment sequenceGSK2798745 CBAD treatment sequence

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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)
  • 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.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

GSK Investigational Site

Overland Park, Kansas, 66211, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

long-chain-aldehyde dehydrogenase

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Study Officials

  • GSK Clinical Trials

    GlaxoSmithKline

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 4, 2016

First Posted

October 6, 2016

Study Start

October 1, 2016

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

January 25, 2017

Record last verified: 2017-01

Locations

US(1)