Infection, Human Immunodeficiency VirusPhase 1NCT01425099
Drug Interaction Study Between Dolutegravir and Prednisone
A Phase 1 study testing Dolutegravir and Prednisone in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 1 site in United States.
Trial summary
Dolutegravir (DTG, GSK1349572 is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of human immunodeficiency virus (HIV) infection. DTG is primarily metabolized by UDP-glucuronosyltransferase (UGT1A1) with cytochrome P450 (CYP)3A4 pathway as a minor route. Read more about this study
- 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?
- Dolutegravir and Prednisone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Oct 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 1.5xULN (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 ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- 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 of child-bearing potential and agrees to use one of the contraception methods listed in the protocol. 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 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.
Show all 18Show fewer
- 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, lower or upper GI bleed, inflammatory bowel disease or pancreatitis should be excluded.
- History of glaucoma, psychiatric illness, diabetes or borderline diabetes (or gestational diabetes), hypertension or other disorder that may be made worse by corticosteroid administration.
- 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 at screening visit 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.
- Exclusion criteria for screening ECG as listed in the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Adaptive, Two Part, Two Period, Single Sequence, Drug Interaction Study Between Dolutegravir 50 mg and Prednisone in Adult Healthy Volunteers
Dolutegravir (DTG, GSK1349572 is an integrase inhibitor that is currently in Phase 3 clinical development for the treatment of human immunodeficiency virus (HIV) infection. DTG is primarily metabolized by UDP-glucuronosyltransferase (UGT1A1) with cytochrome P450 (CYP)3A4 pathway as a minor route. Corticosteroids have demonstrated induction effects on UGTs and CYP3A4. Corticosteroids are often used in HIV-infected subjects and have the potential to reduce DTG exposure due to enzyme induction when co-administered. The primary objective of this study is to determine whether concomitant prednisone administration can affect the pharmacokinetics (PK) of DTG.
The study is a two part, two period, open label study. Part 1 will evaluate the effect of a high prednisone dose on DTG PK with the potential for an additional Part 2 depending on the results from Part 1. In Part 1, approximately 12 healthy subjects will receive DTG 50mg q24h for 5 days in Period 1. Subjects will then be administered DTG 50mg q24h in combination with prednisone 60mg for 5 days followed by a 5 day taper (total duration of 10 days) in Period 2. PK data of DTG will be obtained from Part 1 and used to inform decision making on the need for Part 2. If DTG exposure is reduced by more than 50% in Part 1, Part 2 will be carried out where a second cohort of subjects will receive DTG 50mg q24h DTG for 5 days in Period 1 followed by DTG 50mg q24h in combination with prednisone 20mg for 5 days followed by a 5 day taper (total duration of 10 days) in Period 2. Safety evaluations and serial PK samples for DTG will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug. All doses of study drugs will be taken following a moderate fat meal. This study will be conducted at one center in the United States, with healthy adult male and female subjects.
- Conditions
- Infection, Human Immunodeficiency Virus
- Being tested
- Dolutegravir, Prednisone
- 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.
DolutegravirDrug
Also called GSK1349572
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.
PrednisoneDrug
Prednisone is a commonly used corticosteroid used for a variety of medical condiitons
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | In Part 1, approximately 12 healthy subjects will receive DTG 50mg q24h for 5 days in Period 1. Subjects will then be administered DTG 50mg q24h in combination with prednisone 60mg for 5 days followed by a 5 day taper (60 mg Days 1-5, 50 mg Day 6, 40 mg Day 7, 30 mg Day 8, 20 mg Day 9 and 10 mg Day 10 - total duration of 10 days) in Period 2. There will be a screening visit 30 days before the first dose and a follow-up visit 7-14 days after the last dose of drug. Receives: Drug: Dolutegravir; Drug: Prednisone |
| Part 2 | Experimental | If DTG Cτ is reduced by more than 50% in Part 1, Part 2 will be carried out where a second cohort of subjects will receive DTG 50mg q24h DTG for 5 days in Period 1 followed by DTG 50mg q24h in combination with prednisone 20mg for 5 days followed by a 5 day taper (20 mg Days 1-5, 10 mg Days 6 and 7, 5 mg Days 8-10 - total duration of 10 days) in Period 2. There will be a screening visit 30 days before the first dose and a follow-up visit 7-14 days after the last dose of drug. Receives: Drug: Dolutegravir; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of DTG pharmacokinetic parameters on Day 5 and Day 10: AUC(0-t), Cmax, C0, Ct, Cmin, CL/F, and t½.
Samples will be collected at predose and 1, 2, 3, 4, 8, 12 and 24 hours post dose
Measured: Up to 24 hours post dose on Days 5 and 10
Secondary outcomes (1)
Safety and tolerability parameters as assessed by change from baseline in vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2011 (estimated)
- Study startSep 2011
- Primary completionOct 2011
- Study completionOct 2011
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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 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
- NCT01425099
- Sponsor's protocol ID
- 115696
- Status last verified
- Oct 2011
- First submitted
- 18 Aug 2011
- Last updated
- 7 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Song IH, Borland J, Chen S, Savina P, Peppercorn AF, Piscitelli S. Effect of prednisone on the pharmacokinetics of the integrase inhibitor dolutegravir. Antimicrob Agents Chemother. 2013 Sep;57(9):4394-7. doi: 10.1128/AAC.00728-13. Epub 2013 Jul 1.
PubMed 23817375
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Adaptive, Two Part, Two Period, Single Sequence, Drug Interaction Study Between Dolutegravir 50 mg and Prednisone in Adult Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01425099
- Acronym / sponsor ID
- 115696
- Conditions
- Infection, Human Immunodeficiency Virus
- 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
- Sep 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 29 Aug 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 that is currently in Phase 3 clinical development for the treatment of human immunodeficiency virus (HIV) infection. DTG is primarily metabolized by UDP-glucuronosyltransferase (UGT1A1) with cytochrome P450 (CYP)3A4 pathway as a minor route. Corticosteroids have demonstrated induction effects on UGTs and CYP3A4. Corticosteroids are often used in HIV-infected subjects and have the potential to reduce DTG exposure due to enzyme induction when co-administered. The primary objective of this study is to determine whether concomitant prednisone administration can affect the pharmacokinetics (PK) of DTG.
The study is a two part, two period, open label study. Part 1 will evaluate the effect of a high prednisone dose on DTG PK with the potential for an additional Part 2 depending on the results from Part 1. In Part 1, approximately 12 healthy subjects will receive DTG 50mg q24h for 5 days in Period 1. Subjects will then be administered DTG 50mg q24h in combination with prednisone 60mg for 5 days followed by a 5 day taper (total duration of 10 days) in Period 2. PK data of DTG will be obtained from Part 1 and used to inform decision making on the need for Part 2. If DTG exposure is reduced by more than 50% in Part 1, Part 2 will be carried out where a second cohort of subjects will receive DTG 50mg q24h DTG for 5 days in Period 1 followed by DTG 50mg q24h in combination with prednisone 20mg for 5 days followed by a 5 day taper (total duration of 10 days) in Period 2. Safety evaluations and serial PK samples for DTG will be collected during each treatment period. A follow-up visit will occur 7-14 days after the last dose of study drug. All doses of study drugs will be taken following a moderate fat meal. This study will be conducted at one center in the United States, with healthy adult male and female subjects.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Dolutegravir, Drug: PrednisoneIn Part 1, approximately 12 healthy subjects will receive DTG 50mg q24h for 5 days in Period 1. Subjects will then be administered DTG 50mg q24h in combination with prednisone 60mg for 5 days followed by a 5 day taper (60 mg Days 1-5, 50 mg Day 6, 40 mg Day 7, 30 mg Day 8, 20 mg Day 9 and 10 mg Day 10 - total duration of 10 days) in Period 2. There will be a screening visit 30 days before the first dose and a follow-up visit 7-14 days after the last dose of drug. |
| Part 2 | Experimental | Drug: Dolutegravir, Drug: PrednisoneIf DTG Cτ is reduced by more than 50% in Part 1, Part 2 will be carried out where a second cohort of subjects will receive DTG 50mg q24h DTG for 5 days in Period 1 followed by DTG 50mg q24h in combination with prednisone 20mg for 5 days followed by a 5 day taper (20 mg Days 1-5, 10 mg Days 6 and 7, 5 mg Days 8-10 - total duration of 10 days) in Period 2. There will be a screening visit 30 days before the first dose and a follow-up visit 7-14 days after the last dose of drug. |
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 1.5xULN (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 ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- 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 of child-bearing potential and agrees to use one of the contraception methods listed in the protocol. 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 BMI within the range 18.5- 31.0 kg/m2 (inclusive).
Key exclusion criteria (18 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 |
|---|---|---|
| DolutegravirAlso: GSK1349572Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV. | Drug | Part 1, Part 2 |
| PrednisonePrednisone is a commonly used corticosteroid used for a variety of medical condiitons | Drug | Part 1, Part 2 |
Primary outcome
Composite of DTG pharmacokinetic parameters on Day 5 and Day 10: AUC(0-t), Cmax, C0, Ct, Cmin, CL/F, and t½.
Time frame: Up to 24 hours post dose on Days 5 and 10
Samples will be collected at predose and 1, 2, 3, 4, 8, 12 and 24 hours post dose
1 secondary outcome
Safety and tolerability parameters as assessed by change from baseline in vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests
Time frame: 4 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 7 Nov 2011.
- Derived from this study: PubMed 23817375Song IH, Borland J, Chen S, Savina P, Peppercorn AF, Piscitelli S. Effect of prednisone on the pharmacokinetics of the integrase inhibitor dolutegravir. Antimicrob Agents Chemother. 2013 Sep;57(9):4394-7. doi: 10.1128/AAC.00728-13. Epub 2013 Jul 1.
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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 and Prednisone in people with Infection, Human Immunodeficiency Virus, 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 18 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 7 Nov 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?
Composite of DTG pharmacokinetic parameters on Day 5 and Day 10: AUC(0-t), Cmax, C0, Ct, Cmin, CL/F, and t½. (time frame: Up to 24 hours post dose on Days 5 and 10). 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 NCT01425099, 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 7 Nov 2011.