Infections, Human Immunodeficiency Virus and TuberculosisPhase 1NCT01214993
A Phase 1, Open Label, Placebo-Controlled Study to Evaluate the Effect of GSK1349572 on Iohexol and Para-Aminohippurate Clearance in Healthy Subjects
A Phase 1 study testing GSK1349572, Iohexol Injection and Para-aminohippurate infusion in people with Infections, Human Immunodeficiency Virus and Tuberculosis, run by ViiV Healthcare at 1 site in United States.
Trial summary
The current study is designed to confirm the mechanism behind the increase in serum creatinine observed during GSK1349572 therapy; specifically, the study will determine whether GSK1349572 has any effect on glomerular filtration rate (GFR) or effective renal plasma flow. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Infections, Human Immunodeficiency Virus and Tuberculosis
- What is being tested?
- GSK1349572, Iohexol Injection and Para-aminohippurate infusion
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Nov 2010
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects with normal renal function defined as creatinine clearance greater than or equal to 80 mL/min/1.73m2 measured by 24 urine collection
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Male or female between 18 and 65 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 in the protocol 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 the follow-up visit.
- Body weight greater than or equal to 50 kg for males and 45 kg for females and body mass index (BMI) within the range 18.5- 31.0 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- 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.
- 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).
- 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. A subject with any history of allergic reaction to contrast media should not be enrolled.
- 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.
- If heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
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- Has a history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
- Pregnant females as determined by positive serum or urine human chorionic gonadotrophin (hCG) test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- 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, peptic ulceration, inflammatory bowel disease or pancreatitis should be excluded.
- History/evidence of clinically significant pulmonary disease.
- History of significant renal or hepatobiliary diseases. Subjects with a history of nephrolithiasis will be excluded.
- Any subject with evidence of microalbuminuria at screening defined as albumin-to-creatinine ratio in a random spot urine ≥ 0.03 mg/mg OR 30 mg/g.
- History of severe or serious psychiatric disease ever requiring hospitalization, history of suicidal ideation or suicidal attempt, or undergoing psychiatric treatment will be excluded from study participation.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- History of Gilbert's disease.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects.
Trial locations and contacts
1 site in 1 country.
United States1 site
GSK Investigational Site
Minneapolis, Minnesota, 55404
About this study
The current study is designed to confirm the mechanism behind the increase in serum creatinine observed during GSK1349572 therapy; specifically, the study will determine whether GSK1349572 has any effect on glomerular filtration rate (GFR) or effective renal plasma flow. Absent such effects, one may conclude that the small increases in serum creatinine observed are due to the inhibition of the tubular secretion of creatinine via organic cation transporter 2 (OCT2) consistent with in vitro data. .
Read the detailed description
GSK1349572 is an integrase inhibitor being developed for the treatment of human immunodeficiency virus (HIV)-1 infection by GlaxoSmithKline (GSK) on behalf of Shionogi-ViiV Healthcare LLC. In healthy subjects and in dose-ranging clinical trials of GSK1349572, subjects showed a small, reversible increase in serum creatinine concentrations as compared to the control groups; this occurred early during study drug administration and did not progress over time. In vitro data demonstrate that GSK1349572 inhibits the organic cation transporter (OCT2), which mediates the tubular secretion of creatinine; drugs such as cimetidine with similar effects on OCT2 lead to a nonpathological increase in creatinine with no effect on glomerular filtration rate (GFR). The current study is designed to confirm the mechanism behind the increase in serum creatinine observed during GSK1349572 therapy; specifically, the study will determine whether GSK1349572 has any effect on GFR or effective renal plasma flow. Absent such effects, one may conclude that the small increases in serum creatinine observed are due to the inhibition of the tubular secretion of creatinine via OCT2.
Subjects will be given GSK1349572 50mg once daily, 50mg twice daily or placebo once daily for 14 days. Changes in the subject's GFR will be measured through administration of iohexol and effective renal plasma flow will be measured using Para-Aminohippurate (PAH) on days -1, 7 and 14. Changes in serum creatinine and other renal biomarkers will be evaluated at baseline and at various time points throughout the study.
- Being tested
- GSK1349572, Placebo, Iohexol Injection, Para-aminohippurate infusion
- Keywords
- GSK1349572, para-aminohippurate, iohexol
- Medical subject headings
- Infections, Acquired Immunodeficiency Syndrome, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1349572Drug
GSK1349572 is an experimental drug in the integrase inhibitor class of drugs to treat human immunodeficiency virus (HIV)
PlaceboDrug
Placebo is a tablet with no drug in it.
Iohexol InjectionDrug
Also called OMNIPAQUE
Iohexol is an FDA approved radiologic contrast medium
Para-aminohippurate infusionDrug
Para-aminohippurate is an agent to measure effective renal plasma flow.
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | There will be a screening visit within 30 days prior to the first dose of study drug. In this treatment arm, all subjects will receive GSK1349572 50mg (two 25mg tablets) q24h for 14 days. Subjects will also receive iohexol and PAH infusions on Days -1, 7 and 14. There will be a follow-up visit 7-10 days after the last dose of study medication. Receives: Drug: GSK1349572; Drug: Iohexol Injection; Drug: Para-aminohippurate infusion |
| Treatment B | Experimental | There will be a screening visit within 30 days prior to the first dose of study drug. In this treatment arm, all subjects will receive GSK1349572 50mg (two 25mg tablets) q12h for 14 days. Subjects will also receive iohexol and PAH infusions on Days -1, 7 and 14. There will be a follow-up visit 7-10 days after the last dose of study medication. Receives: Drug: GSK1349572; Drug: Iohexol Injection; Drug: Para-aminohippurate infusion |
| Treatment C | Placebo comparator | There will be a screening visit within 30 days prior to the first dose of study drug. In this treatment arm, all subjects will receive placebo q24h for 14 days. Subjects will also receive iohexol and PAH infusions on Days -1, 7 and 14. There will be a follow-up visit 7-10 days after the last dose of study medication. Receives: Drug: Placebo; Drug: Iohexol Injection; Drug: Para-aminohippurate infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glomerular Filtration Rate (GFR) as measured by iohexol plasma clearance at days -1, 7 and 14
Measured: 14 days
Secondary outcomes (5)
Serum creatinine, creatinine clearance (CrCL) as measured by 24-hour urine collection, and extra-glomerular creatinine excretion (EGCE) at days -1, 7, 14 and follow-up
Measured: 24 days
Serum concentrations of Cystatin-C, 24-hour urinary excretions of albumin, total protein, beta2-microblobulin, N-acetyl-beta-d-glucosaminidase (NAG) and retinol binding protein at days -1, 7, 14 and at follow-up
Measured: 24 days
Effective renal plasma flow (ERPF) as measured by plasma clearance of Para Aminohippurate (PAH) at days -1, 7 and 14
Measured: 14 days
Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory and vital signs assessments.
Measured: 24 days
Day 14 GSK1349572 PK parameters including area under the concentration curve (AUC)(0-tau), AUC(0-24), concentration (C)max, C0, and Ctau.
Measured: day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infections, Human Immunodeficiency Virus and TuberculosisStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 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
- NCT01214993
- Sponsor's protocol ID
- 114819
- Status last verified
- Jun 2012
- First submitted
- 1 Oct 2010
- Last updated
- 11 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open Label, Placebo-Controlled Study to Evaluate the Effect of GSK1349572 on Iohexol and Para-Aminohippurate Clearance in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01214993
- Acronym / sponsor ID
- 114819
- Keywords
- GSK1349572, para-aminohippurate, iohexol
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Study start
- Oct 2010
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 5 Oct 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.
The current study is designed to confirm the mechanism behind the increase in serum creatinine observed during GSK1349572 therapy; specifically, the study will determine whether GSK1349572 has any effect on glomerular filtration rate (GFR) or effective renal plasma flow. Absent such effects, one may conclude that the small increases in serum creatinine observed are due to the inhibition of the tubular secretion of creatinine via organic cation transporter 2 (OCT2) consistent with in vitro data. .
Detailed description
GSK1349572 is an integrase inhibitor being developed for the treatment of human immunodeficiency virus (HIV)-1 infection by GlaxoSmithKline (GSK) on behalf of Shionogi-ViiV Healthcare LLC. In healthy subjects and in dose-ranging clinical trials of GSK1349572, subjects showed a small, reversible increase in serum creatinine concentrations as compared to the control groups; this occurred early during study drug administration and did not progress over time. In vitro data demonstrate that GSK1349572 inhibits the organic cation transporter (OCT2), which mediates the tubular secretion of creatinine; drugs such as cimetidine with similar effects on OCT2 lead to a nonpathological increase in creatinine with no effect on glomerular filtration rate (GFR). The current study is designed to confirm the mechanism behind the increase in serum creatinine observed during GSK1349572 therapy; specifically, the study will determine whether GSK1349572 has any effect on GFR or effective renal plasma flow. Absent such effects, one may conclude that the small increases in serum creatinine observed are due to the inhibition of the tubular secretion of creatinine via OCT2.
Subjects will be given GSK1349572 50mg once daily, 50mg twice daily or placebo once daily for 14 days. Changes in the subject's GFR will be measured through administration of iohexol and effective renal plasma flow will be measured using Para-Aminohippurate (PAH) on days -1, 7 and 14. Changes in serum creatinine and other renal biomarkers will be evaluated at baseline and at various time points throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Experimental | Drug: GSK1349572, Drug: Iohexol Injection, Drug: Para-aminohippurate infusionThere will be a screening visit within 30 days prior to the first dose of study drug. In this treatment arm, all subjects will receive GSK1349572 50mg (two 25mg tablets) q24h for 14 days. Subjects will also receive iohexol and PAH infusions on Days -1, 7 and 14. There will be a follow-up visit 7-10 days after the last dose of study medication. |
| Treatment B | Experimental | Drug: GSK1349572, Drug: Iohexol Injection, Drug: Para-aminohippurate infusionThere will be a screening visit within 30 days prior to the first dose of study drug. In this treatment arm, all subjects will receive GSK1349572 50mg (two 25mg tablets) q12h for 14 days. Subjects will also receive iohexol and PAH infusions on Days -1, 7 and 14. There will be a follow-up visit 7-10 days after the last dose of study medication. |
| Treatment C | Placebo comparator | Drug: Placebo, Drug: Iohexol Injection, Drug: Para-aminohippurate infusionThere will be a screening visit within 30 days prior to the first dose of study drug. In this treatment arm, all subjects will receive placebo q24h for 14 days. Subjects will also receive iohexol and PAH infusions on Days -1, 7 and 14. There will be a follow-up visit 7-10 days after the last dose of study medication. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects with normal renal function defined as creatinine clearance greater than or equal to 80 mL/min/1.73m2 measured by 24 urine collection
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Male or female between 18 and 65 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 in the protocol 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 the follow-up visit.
Key exclusion criteria (21 listed)
- 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.
- 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).
- 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. A subject with any history of allergic reaction to contrast media should not be enrolled.
- 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.
- If heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
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 |
|---|---|---|
| GSK1349572GSK1349572 is an experimental drug in the integrase inhibitor class of drugs to treat human immunodeficiency virus (HIV) | Drug | Treatment A, Treatment B |
| PlaceboPlacebo is a tablet with no drug in it. | Drug | Treatment C |
| Iohexol InjectionAlso: OMNIPAQUEIohexol is an FDA approved radiologic contrast medium | Drug | Treatment A, Treatment B, Treatment C |
| Para-aminohippurate infusionPara-aminohippurate is an agent to measure effective renal plasma flow. | Drug | Treatment A, Treatment B, Treatment C |
Primary outcome
Glomerular Filtration Rate (GFR) as measured by iohexol plasma clearance at days -1, 7 and 14
Time frame: 14 days
5 secondary outcomes
Serum creatinine, creatinine clearance (CrCL) as measured by 24-hour urine collection, and extra-glomerular creatinine excretion (EGCE) at days -1, 7, 14 and follow-up
Time frame: 24 days
Serum concentrations of Cystatin-C, 24-hour urinary excretions of albumin, total protein, beta2-microblobulin, N-acetyl-beta-d-glucosaminidase (NAG) and retinol binding protein at days -1, 7, 14 and at follow-up
Time frame: 24 days
Effective renal plasma flow (ERPF) as measured by plasma clearance of Para Aminohippurate (PAH) at days -1, 7 and 14
Time frame: 14 days
Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory and vital signs assessments.
Time frame: 24 days
Day 14 GSK1349572 PK parameters including area under the concentration curve (AUC)(0-tau), AUC(0-24), concentration (C)max, C0, and Ctau.
Time frame: day 14
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 11 Jun 2012.
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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, Iohexol Injection and Para-aminohippurate infusion in people with Infections, Human Immunodeficiency Virus and Tuberculosis, 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 7 inclusion and 21 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 11 Jun 2012. 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. Some participants in this study may receive a placebo. 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?
Glomerular Filtration Rate (GFR) as measured by iohexol plasma clearance at days -1, 7 and 14 (time frame: 14 days). 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 11 Jun 2012.