Healthy SubjectsPhase 1NCT01231529
GSK1349572 Hepatic Impairment Study
A Phase 1 study testing GSK1349572 in people with Healthy Subjects and Hepatic Impairment, run by ViiV Healthcare at 1 site in United States.
Trial summary
GSK1349572 is an integrase inhibitor that is currently in clinical development for the treatment of human immunodeficiency virus (HIV) infection. GSK1349572 is metabolized primarily by uridine diphosphate glucuronosyltransferase (UGT)1A1 with a minor role of Cytochrome P450 (CYP)3A. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects, Hepatic Impairment, Infection, Human Immunodeficiency Virus
- What is being tested?
- GSK1349572
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Nov 2010to 4 Jun 2011
- 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
- A male or female is eligible for study participation if he/she: Is healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- OR (Part 1 subjects only) Is considered to have moderate hepatic insufficiency (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having moderate hepatic insufficiency, subjects must have: A Child-Pugh score of 7-9 and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, computed tomography (CT) scan, magnetic resonance imaging (MRI) or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension) OR (Part 2 subjects only) Is considered to have mild hepatic insufficiency (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having mild hepatic insufficiency, subjects must have: A Child-Pugh score of 5-6 and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension).
- Aged between 18 and and 70 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory] or Child-bearing potential and agrees to use one of the contraception methods listed for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 3 days after the last dose of study medication.
- Body weight greater than or equal to 50 kg for men and women and body mass index (BMI) within the range 19- 41 kg/m2 for hepatically impaired subjects; healthy matched control subjects will be matched to BMI +/- 20% and must also remain in the BMI range of 19- 41 kg/m2.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- A healthy subject will not be eligible for inclusion in this study if any of the following criteria apply:
- A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
- A positive test for HIV antibody at screening.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- History of regular alcohol consumption within 6 months of the study defined as: 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.
- 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).
Show all 46Show fewer
- Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.
- Lactating females.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- 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.
- If heparin is used during pharmacokinetic (PK) sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
- Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, 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.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- History of regular use of tobacco or nicotine-containing products within 3 months prior to screening.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5x upper limit of normal (ULN); alkaline phosphatase or bilirubin ≥ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of Gilbert's disease.
- The subject's systolic blood pressure is outside the range of 90-145mmHg, or diastolic blood pressure is outside the range of 45-95mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects.
- Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination) per protocol
- A subject with mild or moderate hepatic impairment will not be eligible for inclusion in this study if any of the following criteria apply:
- 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) are eligible for enrolment.
- A positive test for HIV antibody at screening.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. A positive drug screen will be allowed if it is due to a prescribed medication.
- History of regular alcohol consumption within 6 months of the study defined as: 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.
- 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)
- Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.
- Lactating females.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- 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 GSK Medical Monitor, contraindicates their participation.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
- 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 or gall bladder removal more than three months prior to study) should be excluded.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subjects using any concurrent prohibited medication. Use of common medications which are permitted during the study are listed in the protocol (permitted medications).
- Subjects receiving lactulose who are medically unable to halt lactulose administration from 8h before dosing with study drug to 4h after dosing with study drug.
- Subjects with a change in dose regimen of medically required medication within the 2 weeks prior to dosing.
- Subjects with fluctuating or rapidly deteriorating hepatic function. Assessment of the stability of the subject's hepatic function will be determined by the investigator.
- Subjects with creatinine clearance less than or equal to 50 mL/min (calculated by the Cockcroft-Gault Formula).
- Subjects with advanced ascites (Grade 3).
- Subjects whose serum sodium levels are less than or equal to 125 mmol/L.
- Subjects whose platelets are less than 50,000 x 109/L of blood.
- Subjects with refractory encephalopathy as judged by the investigator or significant Central Nervous System (CNS) disease (e.g. dementia, or seizures) which the investigator considers will interfere with the informed consent, conduct, completion, or results of this trial or constitutes an unacceptable risk to the subject.
- Subjects with signs of active infection.
- Subjects with esophageal variceal bleeding within the past 6 months.
- Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.
- Subjects with any other medical condition which, in the judgement of the investigator and medical monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject.
Trial locations and contacts
1 site in 1 country.
United States1 site
GSK Investigational Site
Minneapolis, Minnesota, 55404
About this study
Official title: A Phase I, Open-Label, Parallel-Group, Two-Part, Adaptive Study to Evaluate the Pharmacokinetics and Safety of GSK1349572 in Subjects With Hepatic Impairment and Healthy Matched Control Subjects (ING113097)
GSK1349572 is an integrase inhibitor that is currently in clinical development for the treatment of human immunodeficiency virus (HIV) infection. GSK1349572 is metabolized primarily by uridine diphosphate glucuronosyltransferase (UGT)1A1 with a minor role of Cytochrome P450 (CYP)3A. Hepatic impairment could potentially alter the clearance and plasma protein binding of GSK1349572. This study will evaluate the single dose pharmacokinetics and safety of GSK1349572 in healthy subjects and in subjects with mild or moderate hepatic impairment based on Child-Pugh category.
This is a single-dose, open-label, parallel group, two-part, adaptive study in adult males and females with mild or moderate hepatic impairment and matched, healthy control subjects with normal hepatic function. Healthy control subjects (16) will be matched for gender, age, and BMI to the subjects in the mild (8) or moderate (8) hepatic impairment category. In Part 1, approximately 8 subjects with moderate hepatic impairment (cohort 1) and 8 matched, control subjects (cohort 2) will each receive GSK1349572 50 mg as a single dose in the fasted state followed by pharmacokinetic sampling for total concentrations of GSK1349572 in plasma. Free (unbound) plasma concentrations of GSK1349572 will also be evaluated at sparse, selected time points. If the geometric mean total plasma area under the concentration curve (AUC) of GSK1349572 is increased by > 2-fold in moderately impaired subjects compared to matched controls, Part 2 will be conducted to evaluate GSK1349572 pharmacokinetics in another group of subjects with mild impairment (8, cohort 3) and matched, control subjects (8, cohort 4). Vital signs, electrocardiograms (ECGs), and adverse events will be monitored throughout the study. A follow-up visit will occur 7-10 days after the dose of study drug.
Read the detailed description
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
- Conditions
- Healthy Subjects, Hepatic Impairment, Infection, Human Immunodeficiency Virus, HIV Infections
- Being tested
- GSK1349572
- Medical subject headings
- Infections, Acquired Immunodeficiency Syndrome, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1349572Drug
All subjects will receive a single dose of GSK1349572 50 mg. GSK1349572 is an experimental drug in the integrase inhibitor class being developed for the treatment of HIV infection. GSK1349572 is not approved by the FDA.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Cohort 1 | Experimental | 8 subjects with moderate hepatic impairment defined by a Child-Pugh score of 7 to 9 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. Receives: Drug: GSK1349572 |
| Part 1 Cohort 2 | Experimental | 8 healthy subjects matched by gender, age and BMI to the subjects in Cohort 1 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. Receives: Drug: GSK1349572 |
| Part 2 Cohort 3 | Experimental | 8 subjects with mild hepatic impairment defined by a Child-Pugh score of 5 to 6 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. This cohort will only be done if the AUC from Cohort 1 is greater than or equal to 2 times the AUC from Cohort 2. Receives: Drug: GSK1349572 |
| Part 2 Cohort 4 | Experimental | 8 healthy subjects matched by gender, age and BMI to the subjects in Cohort 3 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. This cohort will only be done if the AUC from Cohort 1 is greater than or equal to 2 times the AUC from Cohort 2. Receives: Drug: GSK1349572 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC(0-t))
Measured: 72 hours
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity),)
Measured: 72 hours
Maximum observed concentration (Cmax)
Measured: 72 hours
Concentration at 24 hours post dose (C24)
Measured: 24 hours
apparent terminal phase half-life (t1/2)
Measured: 72 hours
apparent clearance (CL/F) following oral dosing
Measured: 72 hours
Apparent volume of distribution after extravascular (e.g., oral) administration (Vz/F)
Measured: 72 hours
Secondary outcomes (10)
Number of subjects with adverse events
Measured: 72 hours
Unbound concentration in plasma of GSK1349572 at 3 hours post dose
Measured: 3 hours
Time of occurrence of Cmax (tmax)
Measured: 24 hours
Number of subjects using concurrent medications
Measured: 72 hours
Change from baseline in clinical laboratory tests
Measured: 72 hours
Change from baseline in vital signs
Measured: 3 hours
Unbound concentration in plasma of GSK1349572 at 24 hours post dose
Measured: 24 hours
Unbound fraction in plasma of GSK1349572 at 3 hours post dose
Measured: 3 hours
Unbound fraction in plasma of GSK1349572 at 24 hours post dose
Measured: 24 hours
Lag time before observation of drug concentrations in sampled matrix (tlag)
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2010 (estimated)
- Study start19 Nov 2010
- Primary completion4 Jun 2011
- Study completion4 Jun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy SubjectsStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe 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 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01231529
- Sponsor's protocol ID
- 113097
- Status last verified
- Jul 2019
- First submitted
- 14 Oct 2010
- Last updated
- 31 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Song IH, Borland J, Savina PM, Chen S, Patel P, Wajima T, Peppercorn AF, Piscitelli SC. Pharmacokinetics of Single-Dose Dolutegravir in HIV-Seronegative Subjects With Moderate Hepatic Impairment Compared to Healthy Matched Controls. Clin Pharmacol Drug Dev. 2013 Oct;2(4):342-348. doi: 10.1002/cpdd.55. Epub 2013 Aug 16.
PubMed 26097786
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Parallel-Group, Two-Part, Adaptive Study to Evaluate the Pharmacokinetics and Safety of GSK1349572 in Subjects With Hepatic Impairment and Healthy Matched Control Subjects (ING113097)
- ClinicalTrials.gov ID
- NCT01231529
- Acronym / sponsor ID
- 113097
- Conditions
- Healthy Subjects, Hepatic Impairment, Infection, Human Immunodeficiency Virus, HIV Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Study start
- 19 Nov 2010 (actual)
- Primary completion
- 4 Jun 2011 (actual)
- Study completion
- 4 Jun 2011 (actual)
- First posted
- 1 Nov 2010 (estimated)
- 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.
GSK1349572 is an integrase inhibitor that is currently in clinical development for the treatment of human immunodeficiency virus (HIV) infection. GSK1349572 is metabolized primarily by uridine diphosphate glucuronosyltransferase (UGT)1A1 with a minor role of Cytochrome P450 (CYP)3A. Hepatic impairment could potentially alter the clearance and plasma protein binding of GSK1349572. This study will evaluate the single dose pharmacokinetics and safety of GSK1349572 in healthy subjects and in subjects with mild or moderate hepatic impairment based on Child-Pugh category.
This is a single-dose, open-label, parallel group, two-part, adaptive study in adult males and females with mild or moderate hepatic impairment and matched, healthy control subjects with normal hepatic function. Healthy control subjects (16) will be matched for gender, age, and BMI to the subjects in the mild (8) or moderate (8) hepatic impairment category. In Part 1, approximately 8 subjects with moderate hepatic impairment (cohort 1) and 8 matched, control subjects (cohort 2) will each receive GSK1349572 50 mg as a single dose in the fasted state followed by pharmacokinetic sampling for total concentrations of GSK1349572 in plasma. Free (unbound) plasma concentrations of GSK1349572 will also be evaluated at sparse, selected time points. If the geometric mean total plasma area under the concentration curve (AUC) of GSK1349572 is increased by > 2-fold in moderately impaired subjects compared to matched controls, Part 2 will be conducted to evaluate GSK1349572 pharmacokinetics in another group of subjects with mild impairment (8, cohort 3) and matched, control subjects (8, cohort 4). Vital signs, electrocardiograms (ECGs), and adverse events will be monitored throughout the study. A follow-up visit will occur 7-10 days after the dose of study drug.
Detailed description
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 Cohort 1 | Experimental | Drug: GSK13495728 subjects with moderate hepatic impairment defined by a Child-Pugh score of 7 to 9 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. |
| Part 1 Cohort 2 | Experimental | Drug: GSK13495728 healthy subjects matched by gender, age and BMI to the subjects in Cohort 1 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. |
| Part 2 Cohort 3 | Experimental | Drug: GSK13495728 subjects with mild hepatic impairment defined by a Child-Pugh score of 5 to 6 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. This cohort will only be done if the AUC from Cohort 1 is greater than or equal to 2 times the AUC from Cohort 2. |
| Part 2 Cohort 4 | Experimental | Drug: GSK13495728 healthy subjects matched by gender, age and BMI to the subjects in Cohort 3 will receive a single oral dose of GSK1349572 50 mg in the morning followed by 72 hour serial PK sampling. There will be a screening visit within 30 days prior to the dose of study drug and a follow-up visit within 7-10 days after the study drug. This cohort will only be done if the AUC from Cohort 1 is greater than or equal to 2 times the AUC from Cohort 2. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- A male or female is eligible for study participation if he/she: Is healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- OR (Part 1 subjects only) Is considered to have moderate hepatic insufficiency (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having moderate hepatic insufficiency, subjects must have: A Child-Pugh score of 7-9 and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, computed tomography (CT) scan, magnetic resonance imaging (MRI) or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension) OR (Part 2 subjects only) Is considered to have mild hepatic insufficiency (of any etiology) and has been clinically stable for at least 1 month prior to screening. To be classified as having mild hepatic insufficiency, subjects must have: A Child-Pugh score of 5-6 and previous confirmation of liver cirrhosis by liver biopsy or other medical imaging technique (including laparoscopy, CT scan, MRI or ultrasonography) associated with an unambiguous medical history (such as evidence of portal hypertension).
- Aged between 18 and and 70 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory] or Child-bearing potential and agrees to use one of the contraception methods listed for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 3 days after the last dose of study medication.
- Body weight greater than or equal to 50 kg for men and women and body mass index (BMI) within the range 19- 41 kg/m2 for hepatically impaired subjects; healthy matched control subjects will be matched to BMI +/- 20% and must also remain in the BMI range of 19- 41 kg/m2.
Key exclusion criteria (46 listed)
- A healthy subject will not be eligible for inclusion in this study if any of the following criteria apply:
- A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
- A positive test for HIV antibody at screening.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- History of regular alcohol consumption within 6 months of the study defined as: 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.
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 |
|---|---|---|
| GSK1349572All subjects will receive a single dose of GSK1349572 50 mg. GSK1349572 is an experimental drug in the integrase inhibitor class being developed for the treatment of HIV infection. GSK1349572 is not approved by the FDA. | Drug | Part 1 Cohort 1, Part 1 Cohort 2, Part 2 Cohort 3, Part 2 Cohort 4 |
Primary outcome
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC(0-t))
Time frame: 72 hours
Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity),)
Time frame: 72 hours
Maximum observed concentration (Cmax)
Time frame: 72 hours
Concentration at 24 hours post dose (C24)
Time frame: 24 hours
apparent terminal phase half-life (t1/2)
Time frame: 72 hours
apparent clearance (CL/F) following oral dosing
Time frame: 72 hours
Apparent volume of distribution after extravascular (e.g., oral) administration (Vz/F)
Time frame: 72 hours
10 secondary outcomes
Number of subjects with adverse events
Time frame: 72 hours
Unbound concentration in plasma of GSK1349572 at 3 hours post dose
Time frame: 3 hours
Time of occurrence of Cmax (tmax)
Time frame: 24 hours
Number of subjects using concurrent medications
Time frame: 72 hours
Change from baseline in clinical laboratory tests
Time frame: 72 hours
Change from baseline in vital signs
Time frame: 3 hours
Unbound concentration in plasma of GSK1349572 at 24 hours post dose
Time frame: 24 hours
Unbound fraction in plasma of GSK1349572 at 3 hours post dose
Time frame: 3 hours
Unbound fraction in plasma of GSK1349572 at 24 hours post dose
Time frame: 24 hours
Lag time before observation of drug concentrations in sampled matrix (tlag)
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2019.
- Background: PubMed 26097786Song IH, Borland J, Savina PM, Chen S, Patel P, Wajima T, Peppercorn AF, Piscitelli SC. Pharmacokinetics of Single-Dose Dolutegravir in HIV-Seronegative Subjects With Moderate Hepatic Impairment Compared to Healthy Matched Controls. Clin Pharmacol Drug Dev. 2013 Oct;2(4):342-348. doi: 10.1002/cpdd.55. Epub 2013 Aug 16.
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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.
GSK Clinical Trials study director
ViiV Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK1349572 in people with Healthy Subjects and Hepatic Impairment, run by ViiV Healthcare at 1 site 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 6 inclusion and 46 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 31 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC(0-t)) (time frame: 72 hours). The study lists 7 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 NCT01231529, 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 31 Jul 2019.