Pharmacokinetics of Single-dose Dolutegravir in HIV-seronegative Subjects With Severe Hepatic Impairment Compared to Matched Controls.

NCT03813979 | Withdrawn Phase 4 DMC

• 1 other identifier: UMCN-AKF-16.03
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, parallel-group, nonrandomized, multi-centre, phase-IV, single dose trial in 8 HIV-seronegative subjects with severe hepatic impairment and 8 matched controls to assess the pharmacokinetics of a single dose of 50mg of dolutegravir in subjects with severe hepatic impairment.

Conditions

HIV-1-infection; Hepatic Impairment

Keywords

pharmacokinetics; dolutegravir

Outcome Measures

Primary Outcomes (1)

• area under the curve

  dolutegravir area under the curve

  24 hours

Secondary Outcomes (1)

• adverse events

  7 days

Study Arms (2)

Hepatic impairment group

EXPERIMENTAL

Dolutegravir in HIV-seronegative subjects with severe hepatic impairment (child-Pugh score 10 or greater)

Drug: Dolutegravir

Matched controls

ACTIVE COMPARATOR

Dolutegravir in control group matched for gender, age and BMI with subjects in hepatic impairment group

Drug: Dolutegravir

Interventions

Dolutegravir DRUG

Intake of a single-dose dolutegravir 50 mg tablet on an empty stomach

Hepatic impairment group; Matched controls

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is at least 18 and not older than 90 years at screening.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Child-Pugh score 10 or greater (Appendix A). Expected to be in clinical stable condition for at least 4 weeks as assessed by the subject's own hepatologist. This assessment takes into account the following aspects: MELD score, fibroscan results (if available), life expectancy, recent history of decompensation events and the rate of progression of hepatic insufficiency.
• For healthy volunteers
• Subject is at least 18 and not older than 90 years at screening.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to Day 1. Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges. If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
• Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.

You may not qualify if:

• Inability to understand the nature and extent of the study and the procedures required.
• Gilbert's syndrome or other underlying disease (other than hepatic impairment) that causes alterations in the Child-Pugh class components (bilirubin, albumin, prothrombin, encephalopathy and ascites).
• Therapy with strong inducers or inhibitors of UGT1A1 or drugs that are contra-indicated with concomitant use of dolutegravir (see appendix B). (NB. there are restrictions for intake of magnesium/aluminium-containing antacids, iron and calcium supplements, multivitamins and other cation-containing supplements (see appendix B and section 5.2)).
• Positive HIV test.
• Participation in a drug study within 60 days prior to Day 1.
• Febrile illness within 3 days before Day 1.
• For healthy volunteers
• Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
• Positive HIV test.
• Positive hepatitis B or C test.
• Pregnant female (as confirmed by an hCG test performed less than 4 weeks before Day 1) or breast-feeding female. Female subjects of childbearing potential without adequate contraception.
• Therapy with strong inducers or inhibitors of UGT1A1 or drugs that are contra-indicated with concomitant use of dolutegravir (see appendix B). (NB. there are restrictions for intake of magnesium/aluminium-containing antacids, iron and calcium supplements, multivitamins and other cation-containing supplements (see appendix B and section 5.2)).
• Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal and hepatic disorders, hormonal disorders (especially diabetes mellitus), coagulation disorders.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• History of or current abuse of drugs, alcohol or solvents.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Erasmus Medical Center: collaborator
• Leiden University Medical Center: collaborator
• University Medical Center Groningen: collaborator

MeSH Terms

Interventions

dolutegravir

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: January 23, 2019
• Study Start: November 15, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: June 10, 2021

Record last verified: 2021-06