Infections, Human Immunodeficiency Virus and HerpesviridaePhase 1NCT01382238
Relative Bioavailability Study of a Pediatric Granule Formulation of Dolutegravir
A Phase 1 study testing Dolutegravir 50 mg tablet and Dolutegravir 50 mg oral granules in people with Infections, Human Immunodeficiency Virus and Herpesviridae, run by ViiV Healthcare at 1 site in United States.
Trial summary
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor currently in Phase 3 clinical trials for the treatment of human immunodeficiency virus (HIV) infection. A granule formulation has been developed as an alternative to the current tablet formulation for administration in pediatric populations. 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 Herpesviridae
- What is being tested?
- Dolutegravir 50 mg tablet and Dolutegravir 50 mg oral granules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to Aug 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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%). A single repeat is allowed for eligibility determination.
- 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 or child-bearing potential and agrees to use an appropriate contraception method 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 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. - Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.
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- 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.
- 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. A single repeat is allowed for eligibility determination.
- Exclusion criteria for screening ECG within protocol limits.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Relative Bioavailability Study of a Tablet Formulation vs. Pediatric Granule Formulation of Dolutegravir 50 mg and Effect of Different Types of Water Plus Infant Formula on the Pediatric Granule Formulation in Healthy Male and Female Volunteers
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor currently in Phase 3 clinical trials for the treatment of human immunodeficiency virus (HIV) infection. A granule formulation has been developed as an alternative to the current tablet formulation for administration in pediatric populations.
This is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects. The study will evaluate the relative bioavailability of a 50 mg granule formulation of dolutegravir when administered 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula compared to the current 50 mg tablet formulation administered with tap water. Safety evaluations and serial PK samples will be collected during each treatment period. A taste assessment of the granule will also be performed. A follow-up visit will occur 5-7 days after the last dose of study drug.
Pharmacokinetic assessments during the study will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC(0-t)), maximum observed concentration (Cmax), terminal phase half-life (t½), lag time before observation of drug concentrations in sampled matrix (tlag), time of occurrence of Cmax (tmax), concentration at 24 hours post-dose (C24), and apparent clearance following oral dosing (CL/F).
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
- Being tested
- Dolutegravir 50 mg tablet, Dolutegravir 50 mg oral granules
- Keywords
- dolutegravir, pediatric, granule formulation, GSK1349572, HIV
- 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.
Dolutegravir 50 mg tabletDrug
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.
Dolutegravir 50 mg oral granulesDrug
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Subjects will have a screening visit within 30 days prior to the first dose of study drug, five treatment periods containing a single dose of study drug, followed by 48 hours of serial PK collection. In the 5 treatment periods subjects will receive DTG granule formulation 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula. They will also receive the current 50 mg tablet formulation administered with tap water. These treatments will be administered in a random order. Subjects will check out of the unit on Day 3 after the 48 hour PK sample in each period. Study periods will be separated by at least 5 days. Subjects will have a follow-up visit 5-7 days after last dose of DTG given. Receives: Drug: Dolutegravir 50 mg tablet; Drug: Dolutegravir 50 mg oral granules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma DTG AUC(0-infinity), AUC(0-t), and Cmax
Measured: 48 hours post dose
Secondary outcomes (2)
Plasma DTG t½, tlag, tmax, C24, and CL/F
Measured: 48 hours post dose
Safety and tolerability parameters as assessed by change from baseline in 12-lead ECG and vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionAug 2011
- Study completionAug 2011
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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01382238
- Sponsor's protocol ID
- 114556
- Status last verified
- Sep 2011
- First submitted
- 23 Jun 2011
- Last updated
- 19 Sep 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relative Bioavailability Study of a Tablet Formulation vs. Pediatric Granule Formulation of Dolutegravir 50 mg and Effect of Different Types of Water Plus Infant Formula on the Pediatric Granule Formulation in Healthy Male and Female Volunteers
- ClinicalTrials.gov ID
- NCT01382238
- Acronym / sponsor ID
- 114556
- Keywords
- dolutegravir, pediatric, granule formulation, GSK1349572, HIV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- Shionogi, GlaxoSmithKline
- Study start
- Jun 2011
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 27 Jun 2011 (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.
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor currently in Phase 3 clinical trials for the treatment of human immunodeficiency virus (HIV) infection. A granule formulation has been developed as an alternative to the current tablet formulation for administration in pediatric populations.
This is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects. The study will evaluate the relative bioavailability of a 50 mg granule formulation of dolutegravir when administered 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula compared to the current 50 mg tablet formulation administered with tap water. Safety evaluations and serial PK samples will be collected during each treatment period. A taste assessment of the granule will also be performed. A follow-up visit will occur 5-7 days after the last dose of study drug.
Pharmacokinetic assessments during the study will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC(0-t)), maximum observed concentration (Cmax), terminal phase half-life (t½), lag time before observation of drug concentrations in sampled matrix (tlag), time of occurrence of Cmax (tmax), concentration at 24 hours post-dose (C24), and apparent clearance following oral dosing (CL/F).
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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: Dolutegravir 50 mg tablet, Drug: Dolutegravir 50 mg oral granulesSubjects will have a screening visit within 30 days prior to the first dose of study drug, five treatment periods containing a single dose of study drug, followed by 48 hours of serial PK collection. In the 5 treatment periods subjects will receive DTG granule formulation 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula. They will also receive the current 50 mg tablet formulation administered with tap water. These treatments will be administered in a random order. Subjects will check out of the unit on Day 3 after the 48 hour PK sample in each period. Study periods will be separated by at least 5 days. Subjects will have a follow-up visit 5-7 days after last dose of DTG given. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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%). A single repeat is allowed for eligibility determination.
- 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 or child-bearing potential and agrees to use an appropriate contraception method 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).
Key exclusion criteria (16 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 |
|---|---|---|
| Dolutegravir 50 mg tabletDolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV. | Drug | Single arm |
| Dolutegravir 50 mg oral granulesDolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV. | Drug | Single arm |
Primary outcome
Plasma DTG AUC(0-infinity), AUC(0-t), and Cmax
Time frame: 48 hours post dose
2 secondary outcomes
Plasma DTG t½, tlag, tmax, C24, and CL/F
Time frame: 48 hours post dose
Safety and tolerability parameters as assessed by change from baseline in 12-lead ECG and vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests
Time frame: 6 weeks
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 19 Sep 2011.
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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 Dolutegravir 50 mg tablet and Dolutegravir 50 mg oral granules 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 16 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 19 Sep 2011. 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 DTG AUC(0-infinity), AUC(0-t), and Cmax (time frame: 48 hours post dose). 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 19 Sep 2011.