HIV-1-infectionPhase 4POLONCT03813979
Pharmacokinetics of Single-dose Dolutegravir in HIV-seronegative Subjects With Severe Hepatic Impairment Compared to Matched Controls.
A Phase 4 study testing Dolutegravir in people with HIV-1-infection and Hepatic Impairment, run by Radboud University Medical Center.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV-1-infection, Hepatic Impairment
- What is being tested?
- Dolutegravir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Nov 2020to 31 Dec 2021
- Phase
- Phase 4
- 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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- Inability to understand the nature and extent of the study and the procedures required.
- Participation in a drug study within 60 days prior to Day 1.
- Donation of blood within 60 days prior to Day 1.
- Febrile illness within 3 days before Day 1
- UGT1A1 polymorphism (at least one *28, *37 or *6 allele) -
About this study
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.
Read the detailed description
This is an open-label, parallel-group, nonrandomized, multi-centre, phase-IV, single dose trial. The primary aim of this study is to assess the pharmacokinetics of a single dose of 50mg of dolutegravir in HIV-seronegative subjects with severe hepatic impairment (n=8) and compare these with a single dose of 50mg of dolutegravir in matched controls (n=8). In both groups a pharmacokinetic (PK) curve will be recorded for determination of dolutegravir (and dolutegravir-glucuronide).
- Conditions
- HIV-1-infection, Hepatic Impairment
- Being tested
- Dolutegravir
- Keywords
- pharmacokinetics, dolutegravir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Intake of a single-dose dolutegravir 50 mg tablet on an empty stomach
| Study group | Role | What they receive |
|---|---|---|
| Hepatic impairment group | Experimental | Dolutegravir in HIV-seronegative subjects with severe hepatic impairment (child-Pugh score 10 or greater) Receives: Drug: Dolutegravir |
| Matched controls | Active comparator | Dolutegravir in control group matched for gender, age and BMI with subjects in hepatic impairment group Receives: Drug: Dolutegravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
area under the curve
dolutegravir area under the curve
Measured: 24 hours
Secondary outcomes (1)
adverse events
number and severity of adverse events
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2019
- Study start15 Nov 2020 (estimated)
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Why it stopped: difficult recruitment and delay due to COVID19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, Leiden University Medical Center, University Medical Center Groningen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03813979
- Sponsor's protocol ID
- UMCN-AKF-16.03
- Acronym
- POLO
- Status last verified
- Jun 2021
- First submitted
- 21 Jan 2019
- Last updated
- 10 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Single-dose Dolutegravir in HIV-seronegative Subjects With Severe Hepatic Impairment Compared to Matched Controls.
- ClinicalTrials.gov ID
- NCT03813979
- Acronym / sponsor ID
- POLO / UMCN-AKF-16.03
- Conditions
- HIV-1-infection, Hepatic Impairment
- Keywords
- pharmacokinetics, dolutegravir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: difficult recruitment and delay due to COVID19
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, Leiden University Medical Center, University Medical Center Groningen
- Study start
- 15 Nov 2020 (estimated)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 23 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an open-label, parallel-group, nonrandomized, multi-centre, phase-IV, single dose trial. The primary aim of this study is to assess the pharmacokinetics of a single dose of 50mg of dolutegravir in HIV-seronegative subjects with severe hepatic impairment (n=8) and compare these with a single dose of 50mg of dolutegravir in matched controls (n=8). In both groups a pharmacokinetic (PK) curve will be recorded for determination of dolutegravir (and dolutegravir-glucuronide).
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hepatic impairment group | Experimental | Drug: DolutegravirDolutegravir in HIV-seronegative subjects with severe hepatic impairment (child-Pugh score 10 or greater) |
| Matched controls | Active comparator | Drug: DolutegravirDolutegravir in control group matched for gender, age and BMI with subjects in hepatic impairment group |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DolutegravirIntake of a single-dose dolutegravir 50 mg tablet on an empty stomach | Drug | Hepatic impairment group, Matched controls |
Primary outcome
area under the curve
Time frame: 24 hours
dolutegravir area under the curve
1 secondary outcome
adverse events
Time frame: 7 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dolutegravir in people with HIV-1-infection and Hepatic Impairment, run by Radboud University Medical Center.
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 8 inclusion and 20 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: withdrawn, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
area under the curve (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jun 2021.