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HIV InfectionsPhase 1NCT02354950

A Study to Evaluate Pharmacokinetic (PK) and Safety of GSK1265744 in Subjects With Hepatic Impairment and Control Healthy Volunteers

A Phase 1 study testing GSK1265744 30mg in people with HIV Infections, run by ViiV Healthcare at 3 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

This will be a Phase 1, open-label, parallel group, two-part, single-dose adaptive study in adults with moderate and mild (if needed) hepatic impairment and matched, healthy control subjects with normal hepatic function. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
HIV Infections
What is being tested?
GSK1265744 30mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
3 sitesUnited States
Study dates
22 Jun 2015to 16 Sep 2016
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 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Hepatic Impaired Subjects (Cohort 1 and 3)
  • Between 18 and 70 years of age
  • Part 1 subjects with Moderate Hepatic Impairment Only (Cohort 1):
  • Subject is considered to have moderate hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. Having moderate hepatic impairment with a Child-Pugh score of 7-9 and previous confirmation of liver cirrhosis.
  • Part 2 subjects with Mild Hepatic Impairment Only (Cohort 3):
  • Subject is considered to have mild hepatic impairment (of any etiology) and has been clinically stable for at least 1 month prior to screening. Having mild hepatic impairment, with a Child-Pugh score of 5-6 and previous confirmation of chronic liver disease.
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  • Supplemental inclusion criteria for all hepatically impaired subjects: Chronic (>6 months), stable (no acute episodes of illness within the previous 1 month prior to screening due to deterioration in hepatic function) hepatic impairment due to any etiology. Subjects must also remain stable throughout the Screening period. - Body weight >=50 kilogram (kg) and BMI within the range 19 - 41 kilogram per meter square (kg/m^2) (inclusive).
  • Male or female: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and the protocol.
  • Healthy control subjects will be matched for age +/-10 years to subjects in the respective hepatic impairment cohort but must also remain in the age range between 18 and 70 years inclusive, at the time of signing the informed consent.
  • Healthy as determined by the investigator or medically qualified designee. Healthy control subjects will be matched for BMI +/-25 percent to subjects in the respective hepatic impairment cohort but must also remain in the range of: Body weight >=50 kg and BMI within the range 19 - 41 kg/m^2 (inclusive)
  • Male or female: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Who cannot join

  • Exclusion Criteria for Hepatic Impaired Subjects (Cohort 1 and 3):
  • Presence of Grade 3 or 4 elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin; corrected QT interval (QTc) > 480 milliseconds (msec);
  • The subject's systolic BP is outside the range of 90-160 millimeter of mercury (mmHg), or diastolic BP is outside the range of 45-95mmHg or heart rate is outside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects
  • Evidence of previous myocardial infarction in the past 12 months or any clinically significant active cardiovascular disease that, in the opinion of the investigator, could interfere with the safety of the subject.
  • Any clinically significant conduction abnormality
  • Any significant arrhythmia.
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  • Non-sustained or sustained ventricular tachycardia.
  • Evidence of recent infection with Hepatitis B and/or Hepatitis C within preceding 6 months. Subjects with chronic Hepatitis B or C (duration>6 months)
  • Subjects with a pre-existing condition (except hepatic impairment) interfering with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy and inflammatory bowel disease should be excluded.
  • Subjects with a history of peptic ulceration or pancreatitis within the preceding 6 months of screening should be excluded.
  • Subjects with previous gastrointestinal (GI) surgery (except appendectomy more than three months prior to study) should be excluded.
  • Subjects with creatinine clearance (CLCR) <=60 milliliter per minute (mL/min) (calculated by the Modification of Diet in Renal Disease [MDRD] equation).
  • Subjects with advanced ascites (Grade 3 or 4).
  • Subjects with refractory encephalopathy as judged by the investigator or significant Central Nervous System (CNS) disease.
  • History of gastric or esophageal variceal bleeding within the past 6 months;
  • Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement;
  • Presence of hepatopulmonary or hepatorenal syndrome;
  • Presence of primarily cholestatic liver diseases;
  • History of liver transplantation;
  • Subjects with signs of active infection;
  • Subjects with unstable cardiac function or subjects with hypertension whose blood pressure is not controlled;
  • Diabetic subjects whose diabetes is not controlled;
  • Subjects with any other medical condition (other than hepatic impairment) which, in the judgment of the investigator and medical monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject;
  • Subjects requiring any concurrent prohibited medication listed in study protocol;
  • Subjects receiving lactulose who are medically unable to halt lactulose administration from 8 hours before dosing with study drug to 4 hours after dosing with study drug;
  • Subjects with a change in dose regimen of medically required medication within the 2 weeks prior to dosing;
  • History of regular alcohol consumption within 6 months of the study;
  • Inability or unwillingness to comply with lifestyle and/or dietary restrictions outlined in protocol;
  • 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. ;
  • Unwillingness or inability to follow the procedures outlined in the protocol;
  • A positive pre-study drug/alcohol screen;
  • A positive test for human immunodeficiency virus (HIV) antibody;
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period;
  • Subject's with a platelet count <50,000 x 10^9 per liter (/L) of blood who have had a major bleeding episode within the past 6 months;
  • Subjects with electrolyte imbalance;
  • 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, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exclusion Criteria for Healthy Subjects (Cohorts 2 and 4):
  • ALT and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent). A single repeat is allowed for eligibility determination;
  • Current or chronic history of liver disease;
  • QTc > 450 msec;
  • Exclusion criteria for screening ECG as per study protocol;
  • Systolic BP outside the range of 90-145 mmHg, or diastolic BP outside the range of 45-95 mmHg or heart rate outside the range of 50-100 bpm for female subjects or 45-100 bpm for male subjects;
  • Evidence of previous myocardial infarction;
  • Any clinically significant conduction abnormality;
  • Any significant arrhythmia.
  • Non-sustained or sustained ventricular tachycardia;
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy and inflammatory bowel disease. Subjects with a history of peptic ulceration or pancreatitis within 6 months of screening. Subjects with previous GI surgery (except appendectomy more than three months prior to study).
  • The use of any concurrent prohibited medications as outlined in study protocol.
  • History of regular alcohol consumption within 6 months of the study,
  • Inability or unwillingness to comply with lifestyle and/or dietary restrictions outlined in study protocol.
  • 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.
  • Unwillingness or inability to follow the procedures outlined in study protocol.
  • Presence of hepatitis B surface antigen (HBsAg) (or positive hepatitis B core antibody with negative hepatitis B surface antibody) or positive hepatitis C antibody test result.
  • A positive pre-study drug/alcohol screen.
  • A positive test for HIV antibody.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • 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, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • GSK Investigational Site

    Lakewood, Colorado, 80228

  • GSK Investigational Site

    Minneapolis, Minnesota, 55404

  • GSK Investigational Site

    Orlando, Florida, 32809

Other trials in United States

About this study

Official title: A Phase I Study to Evaluate the Pharmacokinetics and Safety of GSK1265744 in Subjects With Hepatic Impairment and Healthy Matched Control Subjects

This will be a Phase 1, open-label, parallel group, two-part, single-dose adaptive study in adults with moderate and mild (if needed) hepatic impairment and matched, healthy control subjects with normal hepatic function. In Part 1, healthy control subjects (n=8) matched to subjects with moderate (n=8) hepatic impairment will be enrolled. If the geometric mean total plasma area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of GSK1265744 is increased by >2-fold in moderately impaired subjects relative to matched controls, Part 2 will be conducted to evaluate GSK1265744 PK in subjects with mild hepatic impairment (n=8) and matched, control subjects (n=8). All subjects will receive a single 30 milligram (mg) oral dose of GSK1265744. The primary objective of the study is to compare plasma PK parameters of GSK1265744 in subjects with hepatic impairment to healthy controls matched in gender, age, and body mass index (BMI).

Conditions
HIV Infections
Being tested
GSK1265744 30mg
Keywords
GSK1265744, healthy controls, pharmacokinetic, Hepatic Impairment
Medical subject headings
HIV Infections

What participants receive

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

  • GSK1265744 30mgDrug

    GSK1265744 30mg tablets are white to almost white coated oval tablets. All subjects will receive GSK1265744 30mg as a single oral dose in the fasted state followed by PK sampling.

Study groups in NCT02354950
Study groupRoleWhat they receive
Part 1 Cohort 1 (Moderate hepatic impairment subjects)ExperimentalSubjects with moderate hepatic impairment will receive GSK1265744 30mg as a single oral dose in the fasted state followed by pharmacokinetic sampling for total concentrations of GSK1265744 in plasma
Receives: Drug: GSK1265744 30mg
Part 1 Cohort 2 (Healthy control subjects)ExperimentalHealthy control subjects will receive GSK1265744 30mg as a single oral dose in the fasted state followed by pharmacokinetic sampling for total concentrations of GSK1265744 in plasma
Receives: Drug: GSK1265744 30mg
Part 2 Cohort 3 (Mild hepatic impairment subjects)ExperimentalSubjects with mild hepatic impairment will receive GSK1265744 30mg as a single oral dose in the fasted state followed by pharmacokinetic sampling for total concentrations of GSK1265744 in plasma
Receives: Drug: GSK1265744 30mg
Part 2 Cohort 4 (Healthy control subjects)ExperimentalHealthy control subjects will receive GSK1265744 30mg as a single oral dose in the fasted state followed by pharmacokinetic sampling for total concentrations of GSK1265744 in plasma
Receives: Drug: GSK1265744 30mg

What is being measured

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

  1. Plasma area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)] following a single oral dose of GSK1265744

    Plasma PK samples (2 mL of blood per sample) will be collected to measure GSK1265744 at the following time points: pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose

    Measured: Pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose (Day 8)

  2. Maximum observed concentration (Cmax) following a single oral dose of GSK1265744

    Plasma PK samples (2 mL of blood per sample) will be collected to measure GSK1265744 at the following time points: pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose

    Measured: Pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose (Day 8)

Secondary outcomes (6)

  1. Unbound concentration and unbound fraction in plasma of GSK1265744 at 2 and 24 hours post dose

    Blood samples will be collected to measure bound and unbound plasma GSK1265744 concentrations at 2 and 24 hours post dose

    Measured: Up to 24 hours post dose (Day 2)

  2. Composite of PK parameters including AUC(0-t), %AUCex, C24, t1/2, CL/F, tlag, tmax, and Vz/F following a single oral dose of GSK1265744

    PK parameters including plasma area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration [AUC(0-t)], percentage of AUC(0-infinity) obtained by extrapolation (%AUCex), concentration observed at 24-hours post dose (C24), apparent terminal phase half-life (t1/2), apparent clearance (CL/F), lag time before observation of drug concentrations (tlag), time of occurrence of Cmax (tmax) and apparent terminal phase volume of distribution (Vz/F) following a single oral dose of GSK1265744

    Measured: Pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose (Day 8)

  3. Adverse events (AEs) assessment

    An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product

    Measured: Up to Day 14

  4. Composite of Clinical laboratory parameters including hematology, and clinical chemistry

    Assessment of Laboratory parameters will include hematology, and clinical chemistry

    Measured: Up to Day 14

  5. Electrocardiogram (ECG) monitoring

    12-lead ECGs will be performed with the subject in a semi-supine position having rested in this position for at least 10 minutes beforehand

    Measured: Up to Day 2

  6. Composite of Vital signs assessments will include measurement of temperature, systolic and diastolic blood pressure, heart rate and respiratory rate

    Vital signs will be measured in semi-supine position after 10 minutes rest and will include temperature, systolic and diastolic blood pressure (BP), heart rate (HR) and respiratory rate

    Measured: Up to Day 14

Timeline

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

  1. First posted3 Feb 2015 (estimated)
  2. Study start22 Jun 2015
  3. Primary completion16 Sep 2016
  4. Study completion16 Sep 2016

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02354950
Sponsor's protocol ID
201479
Status last verified
Aug 2020
First submitted
29 Jan 2015
Last updated
5 Aug 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Shaik JSB, Ford SL, Lou Y, Zhang Z, Bakshi KK, Tenorio AR, Trezza C, Spreen WR, Patel P. A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of Cabotegravir in Patients With Hepatic Impairment and Healthy Matched Controls. Clin Pharmacol Drug Dev. 2019 Jul;8(5):664-673. doi: 10.1002/cpdd.655. Epub 2019 Feb 27.

    PubMed 30811880

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1265744 30mg in people with HIV Infections, run by ViiV Healthcare at 3 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 11 inclusion and 57 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 5 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

Plasma area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)] following a single oral dose of GSK1265744 (time frame: Pre-dose (within 15 minutes prior to dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose (Day 8)). The study lists 2 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 NCT02354950, 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 5 Aug 2020.

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