Infection, Human Immunodeficiency VirusPhase 1NCT02064374

Effect of Dolutegravir on Metformin Pharmacokinetics in Healthy Adult Subjects

A Phase 1 study testing Metformin 500 mg q12h, Dolutegravir 50 mg q24h and Dolutegravir 50 mg q12h in people with Infection, Human Immunodeficiency Virus, 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: Infection, Human Immunodeficiency Virus
What is being tested?: Metformin 500 mg q12h, Dolutegravir 50 mg q24h and Dolutegravir 50 mg q12h
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteUnited States
Study dates: Feb 2014to May 2014
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

Male/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by a responsible and experienced physician, based on a medical evaluation including [medical history, physical examination, laboratory tests and cardiac monitoring]. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >=50 kilograms (Kg) for males and >=45 Kg for females and body mass index (BMI) within the range 18.5 - 31.0 Kg/m^2 (square meters) (inclusive).
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 [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international units per milliliter (MIU/mL) and estradiol <40 picograms (pg)/mL (<147 picomole per liter (pmol/L) is confirmatory]; Child-bearing potential with negative pregnancy test as determined by [serum or urine] human chorionic gonadotropin (hCG) test at screening or prior to dosing AND Agrees to use one of the contraception methods 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 5 days post-last dose. OR has only same-sex partners, when this is her preferred and usual lifestyle.
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Alanine aminotransferase, alkaline phosphatase and bilirubin <= 1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination.

Who cannot join

A positive pre-study drug/alcohol screen.
A positive test for human immunodeficiency virus (HIV) antibody.
Pregnant females as determined by positive [serum or urine] hCG test at screening or prior to dosing.
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.
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. Subjects will allergy to tricyclic antidepressants should not be enrolled.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

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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).
Lactating females.
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
Unable to refrain from the 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.
The subject's systolic blood pressure is outside the range of 90-140 millimeters of mercury (mmHg), or diastolic pressure is outside the range of 45-90 mmHg, or heart rate is outside the range of 50-100 beats per minute (bpm) for female subjects or 45-100 bpm for male subjects. A single repeat is allowed for eligibility determination.
Exclusion criteria for screening electrocardiogram (ECG) (a single repeat is allowed for eligibility determination): Heart rate for males <45 and >110 bpm and females <50 and >100 bpm; PR interval <120 and >220 msec, QRS duration <70 and >120 msec, QTc interval (Bazett) >450 msec. Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization); any clinically significant arrhythmia which, in the opinion of the investigator and GSK Medical Monitor, will interfere with the safety for the individual subject; any conduction abnormality (including but not specific to left or right incomplete bundle branch block, atrioventricular block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses>3 seconds, and non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

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: A Phase I, Open Label, Parallel Group, Three Period, Fixed Sequence Crossover Study to Evaluate the Effect of Dolutegravir on Metformin Pharmacokinetics in Healthy Adult Subjects

This study will be a phase 1, open label, parallel group, three period crossover study to evaluate the effect of dolutegravir (DTG) on the steady state pharmacokinetics of metformin and on the safety and tolerability of dolutegravir and metformin. Subjects will have a screening visit within 30 days prior to the first dose of study drug, three treatment periods, and a follow up visit 7-14 days after the last dose of study drug. Eligible subjects will be assigned to one of the two treatment cohorts. Subjects will receive metformin 500 milligram (mg) after every 12 hours (q12h) for 5 days in Period 1; metformin 500 mg q12h plus dolutegravir 50 mg after every 24 hours (q24h) (Cohort 1) or 50 mg q12h (Cohort 2) for 7 days in Period 2; and metformin 500 mg q12h for 10 days in Period 3. There will be no washout periods between treatments. All doses of study drug will be taken following a meal. Safety evaluations will be collected during each period. Serial pharmacokinetic (PK) samples will be collected for metformin on the last day of each period and for dolutegravir on the last day of Period 2.

Conditions: Infection, Human Immunodeficiency Virus
Being tested: Metformin 500 mg q12h, Dolutegravir 50 mg q24h, Dolutegravir 50 mg q12h
Keywords: Dolutegravir, drug interaction, metformin, pharmacokinetics, healthy volunteers
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.

Metformin 500 mg q12hDrug
Metformin will be supplied as 500 mg tablet to be administered orally.
Dolutegravir 50 mg q24hDrug
Dolutegravir will be supplied as 50 mg tablet to be administered orally. To be taken once a day in the morning in Period 2 (Total daily dose 50 mg per day for Cohort 1 only)
Dolutegravir 50 mg q12hDrug
Dolutegravir will be supplied as 50 mg tablet to be administered orally. To be taken 50 mg tablets every 12 hours in Period 2 (Total daily dose 100 mg per day for Cohort 2 only).

Study groups in NCT02064374
Study group	Role	What they receive
Cohort 1	Experimental	All subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive Metformin immediate release (IR) 500 mg q12h following a moderate fat meal for 5 days (Period 1), followed by Metformin IR 500 mg q12h plus DTG 50 mg q24h following a moderate fat meal for 7 days (Days 1-7 of Period 2), followed by Metformin IR 500 mg q12h following a moderate fat meal (Days 1-10 of period 3). Receives: Drug: Metformin 500 mg q12h; Drug: Dolutegravir 50 mg q24h
Cohort 2	Experimental	All subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive Metformin IR 500 mg q12h following a moderate fat meal (Day 1-5 of Period 1), followed by Metformin IR 500 mg q12h plus DTG 50 mg q12h following a moderate fat meal for 7 days (Days 1-7 of Period 2), followed by Metformin IR 500 mg q12h following a moderate fat meal (Days 1-10 of period 3). Receives: Drug: Metformin 500 mg q12h; Drug: Dolutegravir 50 mg q12h

What is being measured

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

Steady state plasma metformin pharmacokinetics (PK) parameters
PK parameters will include: maximum concentration (Cmax), area under the time-concentration curve over the dosing interval [AUC(0-tau)]
Measured: Day 5 to Day 22
Steady state plasma DTG PK parameters
PK parameters will include: Area under the time-concentration curve over the dosing interval [AUC(0-tau)], apparent clearance following oral dosing (CL/F), concentration at time zero (C0) and maximum concentration (Cmax)
Measured: Day 12 and Day 13
Steady-state plasma metformin PK parameters in Period 2 as compared to those in Period 1
PK parameters will include: Terminal phase half-life (t1/2) and Apparent clearance following oral dosing (CL/F)
Measured: Day 5 to Day 12

Secondary outcomes (5)

Change from baseline in vital signs
Vital signs will include systolic and diastolic blood pressure and pulse rate.
Measured: Upto Day 22
Number of subjects with adverse events (AEs)
AEs will be assessed throughout the study.
Measured: Upto Day 22
Toxicity grading of clinical laboratory tests
Laboratory assessments will include haematology, clinical chemistry and urinalysis parameters.
Measured: Upto Day 22
Steady-state plasma metformin PK parameters in Period 3 for each cohort
PK parameters will include: Cmax, concentration curve over the dosing interval [AUC(0-tau)], Terminal phase half-life (t1/2) and apparent clearance following oral dosing (CL/F)
Measured: Upto Day 22
Changes in serum creatinine upon dosing and discontinuation of DTG
Serum creatinine change will be calculated from baseline over time in each period
Measured: Upto Day 22

Timeline

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

Feb 2014May 2014

First posted17 Feb 2014 (estimated)
Study startFeb 2014
Primary completionMay 2014
Study completionMay 2014

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 Infection, Human Immunodeficiency VirusStudies 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02064374
Sponsor's protocol ID: 201167
Status last verified: May 2014
First submitted: 13 Feb 2014
Last updated: 26 May 2014
Results posted: No
Data monitoring committee: No

Publications

Song IH, Zong J, Borland J, Jerva F, Wynne B, Zamek-Gliszczynski MJ, Humphreys JE, Bowers GD, Choukour M. The Effect of Dolutegravir on the Pharmacokinetics of Metformin in Healthy Subjects. J Acquir Immune Defic Syndr. 2016 Aug 1;72(4):400-7. doi: 10.1097/QAI.0000000000000983.
PubMed 26974526

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open Label, Parallel Group, Three Period, Fixed Sequence Crossover Study to Evaluate the Effect of Dolutegravir on Metformin Pharmacokinetics in Healthy Adult Subjects
ClinicalTrials.gov ID: NCT02064374
Acronym / sponsor ID: 201167
Conditions: Infection, Human Immunodeficiency Virus
Keywords: Dolutegravir, drug interaction, metformin, pharmacokinetics, healthy volunteers
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Collaborators: GlaxoSmithKline
Study start: Feb 2014
Primary completion: May 2014 (actual)
Study completion: May 2014 (actual)
First posted: 17 Feb 2014 (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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cohort 1	Experimental	Drug: Metformin 500 mg q12h, Drug: Dolutegravir 50 mg q24hAll subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive Metformin immediate release (IR) 500 mg q12h following a moderate fat meal for 5 days (Period 1), followed by Metformin IR 500 mg q12h plus DTG 50 mg q24h following a moderate fat meal for 7 days (Days 1-7 of Period 2), followed by Metformin IR 500 mg q12h following a moderate fat meal (Days 1-10 of period 3).
Cohort 2	Experimental	Drug: Metformin 500 mg q12h, Drug: Dolutegravir 50 mg q12hAll subjects will be assigned to a single-sequence of three treatment periods without washout. Subjects will receive Metformin IR 500 mg q12h following a moderate fat meal (Day 1-5 of Period 1), followed by Metformin IR 500 mg q12h plus DTG 50 mg q12h following a moderate fat meal for 7 days (Days 1-7 of Period 2), followed by Metformin IR 500 mg q12h following a moderate fat meal (Days 1-10 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)

Male/females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by a responsible and experienced physician, based on a medical evaluation including [medical history, physical examination, laboratory tests and cardiac monitoring]. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >=50 kilograms (Kg) for males and >=45 Kg for females and body mass index (BMI) within the range 18.5 - 31.0 Kg/m^2 (square meters) (inclusive).
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 [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international units per milliliter (MIU/mL) and estradiol <40 picograms (pg)/mL (<147 picomole per liter (pmol/L) is confirmatory]; Child-bearing potential with negative pregnancy test as determined by [serum or urine] human chorionic gonadotropin (hCG) test at screening or prior to dosing AND Agrees to use one of the contraception methods 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 5 days post-last dose. OR has only same-sex partners, when this is her preferred and usual lifestyle.
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Key exclusion criteria (14 listed)

A positive pre-study drug/alcohol screen.
A positive test for human immunodeficiency virus (HIV) antibody.
Pregnant females as determined by positive [serum or urine] hCG test at screening or prior to dosing.
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.
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. Subjects will allergy to tricyclic antidepressants 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
Metformin 500 mg q12hMetformin will be supplied as 500 mg tablet to be administered orally.	Drug	Cohort 1, Cohort 2
Dolutegravir 50 mg q24hDolutegravir will be supplied as 50 mg tablet to be administered orally. To be taken once a day in the morning in Period 2 (Total daily dose 50 mg per day for Cohort 1 only)	Drug	Cohort 1
Dolutegravir 50 mg q12hDolutegravir will be supplied as 50 mg tablet to be administered orally. To be taken 50 mg tablets every 12 hours in Period 2 (Total daily dose 100 mg per day for Cohort 2 only).	Drug	Cohort 2

Primary outcome

Steady state plasma metformin pharmacokinetics (PK) parameters
Time frame: Day 5 to Day 22
PK parameters will include: maximum concentration (Cmax), area under the time-concentration curve over the dosing interval [AUC(0-tau)]
Steady state plasma DTG PK parameters
Time frame: Day 12 and Day 13
PK parameters will include: Area under the time-concentration curve over the dosing interval [AUC(0-tau)], apparent clearance following oral dosing (CL/F), concentration at time zero (C0) and maximum concentration (Cmax)
Steady-state plasma metformin PK parameters in Period 2 as compared to those in Period 1
Time frame: Day 5 to Day 12
PK parameters will include: Terminal phase half-life (t1/2) and Apparent clearance following oral dosing (CL/F)

5 secondary outcomes

Change from baseline in vital signs
Time frame: Upto Day 22
Number of subjects with adverse events (AEs)
Time frame: Upto Day 22
Toxicity grading of clinical laboratory tests
Time frame: Upto Day 22
Steady-state plasma metformin PK parameters in Period 3 for each cohort
Time frame: Upto Day 22
Changes in serum creatinine upon dosing and discontinuation of DTG
Time frame: Upto Day 22

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 26 May 2014.
Derived from this study: PubMed 26974526Song IH, Zong J, Borland J, Jerva F, Wynne B, Zamek-Gliszczynski MJ, Humphreys JE, Bowers GD, Choukour M. The Effect of Dolutegravir on the Pharmacokinetics of Metformin in Healthy Subjects. J Acquir Immune Defic Syndr. 2016 Aug 1;72(4):400-7. doi: 10.1097/QAI.0000000000000983.

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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?

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 14 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 26 May 2014. 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?

Steady state plasma metformin pharmacokinetics (PK) parameters (time frame: Day 5 to Day 22). The study lists 3 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 NCT02064374, 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 26 May 2014.