HIV-associated Lipodystrophy SyndromePhase 1NCT01848340

An Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C-GSK1265744 Administered as a Single Oral Dose and a Study to Describe the Pharmacokinetics of a Supratherapeutic Dose of GSK1265744 in Healthy Adult Subjects

A Phase 1 study testing GSK1265744B (sodium salt) containing 14C-GSK1265744B and 150 mg GSK1265744B in people with HIV-associated Lipodystrophy Syndrome, 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

Search all trials

Trial summary

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: HIV-associated Lipodystrophy Syndrome
What is being tested?: GSK1265744B (sodium salt) containing 14C-GSK1265744B and 150 mg GSK1265744B
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 16 participants
Where: 1 siteUnited States
Study dates: May 2013to Jul 2013
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 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
Part A: Male subjects between 30 and 55 years of age at the time of signing the informed consent.
Part B: Male or female between 18 and 60 years of age inclusive, at the time of signing the informed consent.
Parts A and B male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication.
Part B: A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, bilateral salpingo-oophorectomy or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. Woman with child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in protocol for an appropriate period of time prior to the start of dosing. Female subjects must agree to use contraception until 14 days after the last dose of study medication
Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin <= 1.5xUpper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

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Body weight >= 50 kilogram (kg) and body mass index (BMI) within the range 18.5-31.0 kg/meter square (m^2) (inclusive).
Capable of giving written informed consent
Part A only: Available to complete the study (maximum of 21 days confinement in the clinical research unit).
Part A only: A history of regular bowel movements (averaging one or more bowel movements per day).

Who cannot join

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
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 grams (g) of alcohol: 12 ounces [360 millilitre (mL)] of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
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 GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.
Part A only: Subjects who have received a total body radiation dose of greater than 5.0 mSv or exposure to significant radiation (e.g. serial X-ray or computerised topography (CT) scans, barium meal etc.) in the 12 months prior to this study.
Part A only: Any condition that could interfere with the accurate assessment and recovery of radioactivity [14C].

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Part A only: Participation in a clinical trial involving administration of 14C-labelled compound(s) within the last 12 months.
Part A only: 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 must be excluded.
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of 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 test for human immunodeficiency virus (HIV) antibody.
Part B only: Pregnant or lactating females as determined by positive serum or urine Human Chorionic Gonadotropin (hCG) test at screening or prior to dosing.
The subject's systolic blood pressure is outside the range of 90-140 millimetre of mercury (mmHg), or diastolic blood pressure is outside the range of 45-90 mmHg.
History of clinically significant cardiovascular disease including: Heart rate <45 and >100 beats per minute in males and <50 and >100 beats per minute in females. QRS duration >120 milliseconds (msec) and corrected QT interval (QTc) interval B >450 msec in both males and females. Evidence of previous myocardial infarction, 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, any conduction abnormality [including but not specific to left or right complete bundle branch block, atrioventricular (AV) block [2nd degree (type II) or higher], Wolf Parkinson White [WPW] syndrome) or sinus pauses >3 seconds.
Any significant arrhythmia which, in the opinion of the principal Investigator and GSK Medical Monitor, will interfere with the safety for the individual subject. Nonsustained (>=3 consecutive ventricular ectopic beats) or sustained ventricular tachycardia
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 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)
Exposure to more than four new chemical entities within 12 months prior to the first dosing day
Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days 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.
Unwillingness or inability to follow the procedures outlined in the protocol.
Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.

Trial locations and contacts

1 site in 1 country.

United States1 site

GSK Investigational Site
Overland Park, Kansas, 66211

Other trials in United States

About this study

Official title: An Open Label, Non-Randomized, Mass Balance Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C-GSK1265744 Administered as a Single Oral Dose and a Placebo-Controlled, Randomized Study to Describe the Pharmacokinetics of a Supratherapeutic Dose of GSK1265744 in Healthy Adult Subjects

This will be a two-part study in healthy adults. Part A is a phase 1, non-randomized, open label, single-dose, single-centre mass balance study utilizing a radiolabeled dose to investigate the recovery, excretion, and pharmacokinetics of oral GSK1265744 in a cohort of 6 healthy adult male subjects. Subjects will undergo a pre-study screening visit within 30 days of the first dose and those who successfully pass pre-study assessments and meet eligibility criteria will be enrolled into the study to receive the equivalent of a 30 mg dose of GSK1265744 as an oral solution, containing approximately 70 microcuries (mcg Ci) [0.96 millisieverts (mSv)] of radioactivity under fasted conditions. Blood, urine and fecal samples will be collected for a maximum of 504 hours (21 days) following study drug administration. In Part B, approximately 10 healthy male and female subjects will be enrolled to evaluate the single-dose safety, tolerability and PK of supratherapeutic dose of GSK1265744 150 mg compared with placebo. Each subject will receive a single dose of GSK1265744 150 mg or placebo on Day 1 under fasting conditions in the morning. Blood, urine and fecal samples will be collected for 336 hours (14 days) following dosing.

Conditions: HIV-associated Lipodystrophy Syndrome
Being tested: GSK1265744B (sodium salt) containing 14C-GSK1265744B, 150 mg GSK1265744B, Placebo
Keywords: mass balance, GSK1265744, supratherapeutic, integrase inhibitor, healthy volunteer
Medical subject headings: HIV-Associated Lipodystrophy Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK1265744B (sodium salt) containing 14C-GSK1265744BDrug
A white to slightly colored nonsterile crystalline powder for oral solution
150 mg GSK1265744BDrug
This is GSK1265744B (sodium salt of GSK1265744), lactose monohydrate, Microcrystalline cellulose, hypromellose, sodium lauryl sulfate, croscarmellose sodium, magnesium stearate, Opadry film-coating, white OY-S-28876 tablet
PlaceboDrug
Microcrystalline cellulose, Opadry film-coating, white OY-S-28876 tablet

Study groups in NCT01848340
Study group	Role	What they receive
Part A: 14C-GSK1265744 Arm	Experimental	Each subject will receive a single 30 mg oral solution dose of GSK1265744 containing 14C-GSK1265744 of approximately 70 mcgCi (0.96 MSv) of radioactivity. Receives: Drug: GSK1265744B (sodium salt) containing 14C-GSK1265744B
Part B: GSK1265744 Arm	Experimental	In Part B - 8 subjects will be randomised to receive a single dose of GSK1265744 150 mg Receives: Drug: 150 mg GSK1265744B
Part B: Placebo Arm	Placebo comparator	In Part B - 2 subjects will be randomised to receive a single dose of placebo Receives: Drug: Placebo

What is being measured

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

Part A: Percent recovery of total radioactive [14C] GSK1265744 in urine and feces.
Measurement of total radioactivity present in individual samples (plasma, urine, and feces) collected for a minimum of 336 hours (14 days) post dose up to a maximum of 504 hours (21 days).
Measured: Up to 21 days
Part A: Composite of plasma GSK1265744 PK parameters to access total radioactivity in blood
The PK parameters will include: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a profile [AUC (0-t)], Area under the concentration-time curve from time zero (predose) extrapolated to infinite time [AUC (0-infinity)], Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Terminal phase elimination rate constant (lambda z), apparent terminal phase half-life (t1/2), and oral clearance (CL/F) of plasma GSK1265744 and total radioactivity in plasma and blood following single dose.
Measured: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 288, 312 and 336 hours post dose.
Part B: Number of participants with the use of concurrent medication as a measure of safety and tolerability
Measured: Up to 14 days
Part B: Absolute values and changes over time of hematology as a measure of safety and tolerability.
Measured: Up to 14 days
Part B: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability.
Measured: Up to 14 days
Part B: Absolute values and changes over time of urinalysis as a measure of safety and tolerability.
Measured: Up to 14 days
Part B: Absolute values and changes over time of vital signs as a measure of safety and tolerability.
Measured: Up to 14 days
Part B: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability.
Measured: Up to 14 days
Part B: Number of participants with adverse events as a measure of safety and tolerability
Measured: Up to 14 days
Part B: Composite of plasma GSK1265744 PK parameters
Plasma GSK1265744PK parameters following a single-dose administration of 150 mg under fasted conditions will include: AUC (0-t)], AUC (0-infinity), Cmax, tmax, lambda z, t1/2, and oral clearance (CL/F) of plasma
Measured: Up to 14 days

Secondary outcomes (8)

Part A: Blood: Plasma ratio of total drug-related material (radioactivity)
The blood: plasma ratio of total radioactivity (Cb/Cp) will be calculated at each time point by Clinical Statistics at GSK.
Measured: Up to 21 days
Part A: Percent of total radioactivity associated with red blood cells
Percent of total radioactivity associated with red blood cells will be calculated based on radioactivity concentration in plasma and blood and hematocrit count.
Measured: Up to 21 days
Part A: Absolute values and changes over time of hematology as a measure of safety and tolerability.
Measured: Up to 21 days
Part A: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability.
Measured: Up to 21 days
Part A: Absolute values and changes over time of urinalysis as a measure of safety and tolerability.
Measured: Up to 21 days
Part A: Absolute values and changes over time of vital signs as a measure of safety and tolerability.
Measured: Up to 21 days
Part A: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability.
Measured: Up to 21 days
Part A: Number of participants with adverse events as a measure of safety and tolerability
Measured: Up to 21 days

Timeline

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

May 2013Jul 2013

First posted7 May 2013 (estimated)
Study startMay 2013
Primary completionJul 2013
Study completionJul 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HIV-associated Lipodystrophy SyndromeStudies 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: Single group
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01848340
Sponsor's protocol ID: 117008
Status last verified: Oct 2013
First submitted: 2 May 2013
Last updated: 4 Nov 2013
Results posted: No
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 4 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label, Non-Randomized, Mass Balance Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C-GSK1265744 Administered as a Single Oral Dose and a Placebo-Controlled, Randomized Study to Describe the Pharmacokinetics of a Supratherapeutic Dose of GSK1265744 in Healthy Adult Subjects
ClinicalTrials.gov ID: NCT01848340
Acronym / sponsor ID: 117008
Conditions: HIV-associated Lipodystrophy Syndrome
Keywords: mass balance, GSK1265744, supratherapeutic, integrase inhibitor, healthy volunteer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Collaborators: GlaxoSmithKline
Study start: May 2013
Primary completion: Jul 2013 (actual)
Study completion: Jul 2013 (actual)
First posted: 7 May 2013 (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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Part A: 14C-GSK1265744 Arm	Experimental	Drug: GSK1265744B (sodium salt) containing 14C-GSK1265744BEach subject will receive a single 30 mg oral solution dose of GSK1265744 containing 14C-GSK1265744 of approximately 70 mcgCi (0.96 MSv) of radioactivity.
Part B: GSK1265744 Arm	Experimental	Drug: 150 mg GSK1265744BIn Part B - 8 subjects will be randomised to receive a single dose of GSK1265744 150 mg
Part B: Placebo Arm	Placebo comparator	Drug: PlaceboIn Part B - 2 subjects will be randomised to receive a single dose of placebo

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (10 listed)

Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
Part A: Male subjects between 30 and 55 years of age at the time of signing the informed consent.
Part B: Male or female between 18 and 60 years of age inclusive, at the time of signing the informed consent.
Parts A and B male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication.
Part B: A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, bilateral salpingo-oophorectomy or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. Woman with child-bearing potential and is abstinent or agrees to use one of the contraception methods listed in protocol for an appropriate period of time prior to the start of dosing. Female subjects must agree to use contraception until 14 days after the last dose of study medication

Key exclusion criteria (21 listed)

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
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 grams (g) of alcohol: 12 ounces [360 millilitre (mL)] of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
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 GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.
Part A only: Subjects who have received a total body radiation dose of greater than 5.0 mSv or exposure to significant radiation (e.g. serial X-ray or computerised topography (CT) scans, barium meal etc.) in the 12 months prior to this study.

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
GSK1265744B (sodium salt) containing 14C-GSK1265744BA white to slightly colored nonsterile crystalline powder for oral solution	Drug	Part A: 14C-GSK1265744 Arm
150 mg GSK1265744BThis is GSK1265744B (sodium salt of GSK1265744), lactose monohydrate, Microcrystalline cellulose, hypromellose, sodium lauryl sulfate, croscarmellose sodium, magnesium stearate, Opadry film-coating, white OY-S-28876 tablet	Drug	Part B: GSK1265744 Arm
PlaceboMicrocrystalline cellulose, Opadry film-coating, white OY-S-28876 tablet	Drug	Part B: Placebo Arm

Primary outcome

Part A: Percent recovery of total radioactive [14C] GSK1265744 in urine and feces.
Time frame: Up to 21 days
Measurement of total radioactivity present in individual samples (plasma, urine, and feces) collected for a minimum of 336 hours (14 days) post dose up to a maximum of 504 hours (21 days).
Part A: Composite of plasma GSK1265744 PK parameters to access total radioactivity in blood
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 288, 312 and 336 hours post dose.
The PK parameters will include: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a profile [AUC (0-t)], Area under the concentration-time curve from time zero (predose) extrapolated to infinite time [AUC (0-infinity)], Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax), Terminal phase elimination rate constant (lambda z), apparent terminal phase half-life (t1/2), and oral clearance (CL/F) of plasma GSK1265744 and total radioactivity in plasma and blood following single dose.
Part B: Number of participants with the use of concurrent medication as a measure of safety and tolerability
Time frame: Up to 14 days
Part B: Absolute values and changes over time of hematology as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of urinalysis as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of vital signs as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability.
Time frame: Up to 14 days
Part B: Number of participants with adverse events as a measure of safety and tolerability
Time frame: Up to 14 days
Part B: Composite of plasma GSK1265744 PK parameters
Time frame: Up to 14 days
Plasma GSK1265744PK parameters following a single-dose administration of 150 mg under fasted conditions will include: AUC (0-t)], AUC (0-infinity), Cmax, tmax, lambda z, t1/2, and oral clearance (CL/F) of plasma

8 secondary outcomes

Part A: Blood: Plasma ratio of total drug-related material (radioactivity)
Time frame: Up to 21 days
Part A: Percent of total radioactivity associated with red blood cells
Time frame: Up to 21 days
Part A: Absolute values and changes over time of hematology as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of urinalysis as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of vital signs as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability.
Time frame: Up to 21 days
Part A: Number of participants with adverse events as a measure of safety and tolerability
Time frame: Up to 21 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 4 Nov 2013.

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?

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 10 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 4 Nov 2013. 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?

Part A: Percent recovery of total radioactive [14C] GSK1265744 in urine and feces. (time frame: Up to 21 days). The study lists 10 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 NCT01848340.

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 4 Nov 2013.