Infections, Human Immunodeficiency Virus and HerpesviridaePhase 1NCT01098526

GSK1349572 Drug Interaction Study With Efavirenz

A Phase 1 study testing GSK1349572 and Efavirenz in people with Infections, Human Immunodeficiency Virus and Herpesviridae, run by ViiV Healthcare at 1 site 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

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Infections, Human Immunodeficiency Virus and Herpesviridae
What is being tested?: GSK1349572 and Efavirenz
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 16 Mar 2010to 26 May 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

AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (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].
Body weight greater than or equal to 50 kg for males and 45 kg for females and 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 GSK Medical Monitor, contraindicates their participation.
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 symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA) or any clinically significant cardiac disease.
History/evidence of clinically significant pulmonary disease.
History of significant renal or hepatobiliary diseases. Subjects with a history of nephrolithiasis will be excluded.
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 2nd degree or higher AV block.
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
Buffalo, New York, 14202

Other trials in United States

About this study

Official title: A Phase 1, Open Label, Single Sequence, Three Period Study to Evaluate the Single Dose Pharmacokinetics of GSK1349572 100mg Versus 50mg and the Effect of Efavirenz 600mg Once Daily on the Pharmacokinetics, Safety and Tolerability of GSK1349572 50mg Once Daily in Healthy Adult Subjects (ING114005)

GSK1349572 is an integrase inhibitor that is currently in Phase 2 clinical trials for the treatment of HIV infection. As GSK1349572 development progresses, it may be dosed with non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) including efavirenz (EFV, Sustiva). Efavirenz is a known inducer of CYP3A4. GSK1349572 is primarily metabolized via UGT1A1, however it also has a CYP component to its metabolism, thus a drug interaction between GSK1349572 and EFV is likely. A previous study showed that another NNRTI, etravirine which is also a known inducer of CYP3A and UGT, reduced GSK1349572 exposure significantly. GSK1349572 is not an inhibitor or inducer of CYP3A and is not expected to have impact on pharmacokinetics (PK) of EFV.

This study will investigate the dose proportionality between single doses of 50mg and 100mg of GSK1349572 and will compare steady-state plasma PK, safety and tolerability of GSK1349572 50 mg every 24h (q24h) with and without efavirenz 600 mg q24h. Approximately 12 subjects will receive a single dose of GSK1349572 100 mg (Treatment A) in Period 1 followed by a washout of greater than or equal to 6 days. In Period 2 subjects will receive GSK1349572 50mg q24h for 5 days (Treatment B). Subjects will then be administered GSK1349572 50mg q24h in the morning in combination with EFV 600 mg q24h (Treatment C) in the evening for 14 days in Period 3. There will be no washout between Periods 2 and 3. Safety evaluations and serial PK samples for GSK1349572 will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug.

This study will be conducted at one center in the US, with healthy adult male and female subjects.

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: Infections, Human Immunodeficiency Virus and Herpesviridae
Being tested: GSK1349572, Efavirenz
Keywords: GSK1349572, efavirenz, integrase, pharmacokinetics
Medical subject headings: Infections, Acquired Immunodeficiency Syndrome

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 under development for the treatment of HIV. It is in the class of integrase inhibitors.
EfavirenzDrug
Also called SUSTIVA. SUSTIVA is a registered trademark of Bristol-Myers Squibb
Efavirenz is a drug that has been approved by the FDA for the treatment of HIV. It is in the class of non-nucleoside reverse trancriptase inhibitors.

Study groups in NCT01098526
Study group	Role	What they receive
Cohort 1	Experimental	Subjects will receive a single dose of GSK1349572 100 mg in Period 1 followed by a washout of at least 6 days. Subjects will then receive GSK1349572 50 mg once a day for 5 days in Period 2. Period 3 will begin immediately after Period 2. In Period 3 subjects will receive GSK1349572 50 mg once a day in the morning and Efavirenz 600 mg once a day at bedtime for 14 days. There will be a screening visit up to 30 days before Period 1 and a follow up visit 7-14 days after the end of Period 3. Receives: Drug: GSK1349572; Drug: Efavirenz

What is being measured

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

Plasma GSK1349572 PK parameters: AUC (0-24)
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Measured: 24 hours
Plasma GSK1349572 PK parameters: Cmax
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Measured: 24 hours
Plasma GSK1349572 PK parameters: C24
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Measured: 24 hours
Plasma GSK1349572 steady-state AUC (0-tau)
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days
Plasma GSK1349572 steady-state Cmax
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days
Plasma GSK1349572 steady-state C0
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days
Plasma GSK1349572 steady-state Ctau
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days
Plasma GSK1349572 steady-state Cmin
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days

Secondary outcomes (7)

Safety and tolerability parameters
Safety and tolerability parameters, including adverse event, concurrent medication, clinical laboratory, ECG, and vital signs assessments.
Measured: 4 weeks
Plasma GSK1349572 single dose PK parameters: tmax
Plasma GSK1349572 single dose PK parameters: tmax and tlag, following administration of GSK1349572 100mg and 50mg.
Measured: 24 hours
Plasma GSK1349572 single dose PK parameters: tlag
Plasma GSK1349572 single dose PK parameters: tmax and tlag, following administration of GSK1349572 100mg and 50mg.
Measured: 24 hours
Plasma GSK1349572 steady-state PK parameters: tmax
Plasma GSK1349572 steady-state PK parameters: tmax, tmin, CL/F, and t½, following 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days
Plasma GSK1349572 steady-state PK parameters: tmin
Plasma GSK1349572 steady-state PK parameters: tmax, tmin, CL/F, and t½, following 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days
Plasma GSK1349572 steady-state PK parameters: CL/F
Plasma GSK1349572 steady-state PK parameters: tmax, tmin, CL/F, and t½, following 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days
Plasma GSK1349572 steady-state PK parameters: t½
Plasma GSK1349572 steady-state PK parameters: tmax, tmin, CL/F, and t½, following 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Measured: 19 days

Timeline

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

16 Mar 201026 May 2010

First posted2 Apr 2010 (estimated)
Study start16 Mar 2010
Primary completion26 May 2010
Study completion26 May 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 HerpesviridaeStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01098526
Sponsor's protocol ID: 114005
Status last verified: Sep 2017
First submitted: 4 Mar 2010
Last updated: 25 Sep 2017
Results posted: No
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open Label, Single Sequence, Three Period Study to Evaluate the Single Dose Pharmacokinetics of GSK1349572 100mg Versus 50mg and the Effect of Efavirenz 600mg Once Daily on the Pharmacokinetics, Safety and Tolerability of GSK1349572 50mg Once Daily in Healthy Adult Subjects (ING114005)
ClinicalTrials.gov ID: NCT01098526
Acronym / sponsor ID: 114005
Conditions: Infections, Human Immunodeficiency Virus and Herpesviridae
Keywords: GSK1349572, efavirenz, integrase, pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Collaborators: Shionogi, GlaxoSmithKline
Study start: 16 Mar 2010 (actual)
Primary completion: 26 May 2010 (actual)
Study completion: 26 May 2010 (actual)
First posted: 2 Apr 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.

This study will be conducted at one center in the US, with healthy adult male and female subjects.

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: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Cohort 1	Experimental	Drug: GSK1349572, Drug: EfavirenzSubjects will receive a single dose of GSK1349572 100 mg in Period 1 followed by a washout of at least 6 days. Subjects will then receive GSK1349572 50 mg once a day for 5 days in Period 2. Period 3 will begin immediately after Period 2. In Period 3 subjects will receive GSK1349572 50 mg once a day in the morning and Efavirenz 600 mg once a day at bedtime for 14 days. There will be a screening visit up to 30 days before Period 1 and a follow up visit 7-14 days after the end of Period 3.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (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].
Body weight greater than or equal to 50 kg for males and 45 kg for females and BMI within the range 18.5- 31.0 kg/m2 (inclusive).

Key exclusion criteria (22 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 GSK Medical Monitor, contraindicates their participation.
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 under development for the treatment of HIV. It is in the class of integrase inhibitors.	Drug	Cohort 1
EfavirenzAlso: SUSTIVA. SUSTIVA is a registered trademark of Bristol-Myers SquibbEfavirenz is a drug that has been approved by the FDA for the treatment of HIV. It is in the class of non-nucleoside reverse trancriptase inhibitors.	Drug	Cohort 1

Primary outcome

Plasma GSK1349572 PK parameters: AUC (0-24)
Time frame: 24 hours
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Plasma GSK1349572 PK parameters: Cmax
Time frame: 24 hours
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Plasma GSK1349572 PK parameters: C24
Time frame: 24 hours
Plasma GSK1349572 PK parameters: AUC(0-24), Cmax, and C24, and dose-normalized AUC(0-24), Cmax, and C24 following single dose administration of 100mg and 50mg.
Plasma GSK1349572 steady-state AUC (0-tau)
Time frame: 19 days
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state Cmax
Time frame: 19 days
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state C0
Time frame: 19 days
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state Ctau
Time frame: 19 days
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.
Plasma GSK1349572 steady-state Cmin
Time frame: 19 days
Plasma GSK1349572 steady-state AUC(0-tau), Cmax, C0, Ctau, and Cmin following administration of GSK1349572 50mg q24h for 5 days and following co-administration with EFV 600mg q24h for 14 days.

7 secondary outcomes

Safety and tolerability parameters
Time frame: 4 weeks
Plasma GSK1349572 single dose PK parameters: tmax
Time frame: 24 hours
Plasma GSK1349572 single dose PK parameters: tlag
Time frame: 24 hours
Plasma GSK1349572 steady-state PK parameters: tmax
Time frame: 19 days
Plasma GSK1349572 steady-state PK parameters: tmin
Time frame: 19 days
Plasma GSK1349572 steady-state PK parameters: CL/F
Time frame: 19 days
Plasma GSK1349572 steady-state PK parameters: t½
Time frame: 19 days

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 25 Sep 2017.

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 and Efavirenz in people with Infections, Human Immunodeficiency Virus and Herpesviridae, 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 22 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 25 Sep 2017. 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?

Plasma GSK1349572 PK parameters: AUC (0-24) (time frame: 24 hours). The study lists 8 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 NCT01098526.

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 25 Sep 2017; AzTrials last refreshed its copy on 6 Nov 2026.