Relative Bioavailability Study of Marketed and Lower Dose Ambrisentan in Healthy Adult Participants

NCT ID: NCT04095286

Last Updated: 2020-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-30
• Study Completion Date: 2019-12-17

Brief Summary

This is a single center, open-label, randomized, single-dose, three-period cross-over study in healthy participants. The aim of this study is to provide clinically relevant information on the pharmacokinetic (PK) and safety profile of a new lower dose formulation ambrisentan (AMB) tablet, which is intended for pediatric use. The study will compare the relative bioavailability of the lower dose tablet, dispersed in water and administered orally, with the reference marketed AMB tablet in healthy adults. The total study duration for each participant is expected to be approximately 9 weeks.

Conditions

Hypertension, Pulmonary

Study Design

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

Study Groups

AMB dispersed in water/AMB oral tablet/reference AMB

Eligible participants will receive a single oral dose of 5 milligram (mg) AMB tablet dispersed in water during treatment period 1 followed by a single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive a single oral dose of reference 5 mg AMB tablet. There will be a washout period of 7 days between doses in each treatment period.

Group Type: EXPERIMENTAL

AMB new formulation (1 mg)

Intervention Type: DRUG

AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.

Reference AMB (5 mg)

Intervention Type: DRUG

AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

AMB oral tablet/reference AMB/AMB dispersed in water

Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3, participants will receive single dose of 5 mg AMB tablet dispersed in water. There will be a washout period of 7 days between doses in each treatment period.

Group Type: EXPERIMENTAL

AMB new formulation (1 mg)

Intervention Type: DRUG

AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.

Reference AMB (5 mg)

Intervention Type: DRUG

AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

Reference AMB/AMB dispersed in water/AMB oral tablet

Eligible participants will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period.

Group Type: EXPERIMENTAL

AMB new formulation (1 mg)

Intervention Type: DRUG

AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.

Reference AMB (5 mg)

Intervention Type: DRUG

AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

AMB dispersed in water/reference AMB/AMB oral tablet

Eligible participants will receive single dose of 5 mg AMB tablet dispersed in water during treatment period 1 followed by single dose of reference 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period.

Group Type: EXPERIMENTAL

AMB new formulation (1 mg)

Intervention Type: DRUG

AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.

Reference AMB (5 mg)

Intervention Type: DRUG

AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

AMB oral tablet/AMB dispersed in water/reference AMB

Eligible participants will receive single dose of 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB tablet dispersed in water in treatment period 2. In treatment period 3 participants will receive single dose of reference 5 mg AMB oral tablet. There will be a washout period of 7 days between doses in each treatment period.

Group Type: EXPERIMENTAL

AMB new formulation (1 mg)

Intervention Type: DRUG

AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.

Reference AMB (5 mg)

Intervention Type: DRUG

AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

Reference AMB/AMB oral/AMB dispersed in water

Eligible participants in this arm will receive single dose of reference 5 mg AMB oral tablet during treatment period 1 followed by single dose of 5 mg AMB oral tablet in treatment period 2. In treatment period 3 participants will receive single dose of 5 mg AMB tablet dispersed in water There will be a washout period of 7 days between doses in each treatment period.

Group Type: EXPERIMENTAL

AMB new formulation (1 mg)

Intervention Type: DRUG

AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.

Reference AMB (5 mg)

Intervention Type: DRUG

AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

Interventions

AMB new formulation (1 mg)

AMB tablets will be available at a unit dose strength of 1 mg. Participants will orally administer 5 tablets of 1 mg unit dose.

Intervention Type: DRUG

Reference AMB (5 mg)

AMB reference tablet will be available as film-coated tablet at unit dose strength of 5 mg. Participants will orally administer 1 tablet of 5 mg unit dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring.
• Average systolic blood pressure between 100-160 millimeter of mercury (mmHg) and diastolic between 55-90 mmHg (inclusive) over 3 readings at Screening.
• Body weight >=50 kilogram (kg) for men and >= 45kg for women, and body mass index (BMI) within the range 18-30 kilogram per meter square (kg/m^2) (inclusive).
• Male participants are eligible to participate if they agree to the following during the study and for at least 13 weeks afterwards corresponding to time needed to eliminate study intervention (5 terminal half-lives) plus an additional 90 days (a spermatogenesis cycle): 1. Refrain from donating sperm plus either 2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR
• Must agree to use contraception/barrier, as follows: Agree to use a male condom; and Female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as described.
• A female participant is eligible to participate if she is not a woman of childbearing potential (WOCBP).
• Capable of giving signed informed consent.

Exclusion Criteria

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
• History or presence of palpitations or tachyarrhythmia.
• Hemoglobin (Hb) below the normal range (Hb <133 grams per liter [g/L] for male participants ; and Hb <114 g/L for female participants).
• Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN)
• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times 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).
• Corrected QT interval (QTc) >450 millisecond (msec).
• Past or intended use of over-the-counter or prescription medication (including vitamins and dietary or herbal supplements but excluding paracetamol <=2 grams/day) within 7 days (or 14 days if the drug is a potential enzyme inhibitor) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless approved by the Investigator in conjunction with GlaxoSmithKline Medical Monitor.
• Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56-day period.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrolment or past participation within 30 days before Screening in any other clinical study involving an investigational study intervention or any other type of medical research.
• Presence of Hepatitis B surface antigen (HBsAg) at Screening or within 3 months prior to first dose of study intervention.
• Positive Hepatitis C antibody test result at Screening or within 3 months prior to first dose of study intervention.
• Positive Hepatitis C Ribonucleic acid (RNA) test result at Screening or within 3 months prior to first dose of study intervention.
• Positive human immunodeficiency virus (HIV) antibody test.
• Positive pre-study drug/alcohol screen.
• Regular use of known drugs of abuse.
• Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Smoking > 5 cigarettes per week (or equivalent) and participants must be able to abstain from smoking for a 24-hour period prior to dose and any time whilst in the clinical unit.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 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

Cambridge, Cambridgeshire, United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

205019

Identifier Type: -

Identifier Source: org_study_id