A Phase 1 interventional study of Tivicay and Rezolsta in HIV, sponsored by St Stephens Aids Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-05-22.
Sponsored by St Stephens Aids Trust · Phase 1, Interventional, and Treatment
The purpose of this study is to look at the levels of three HIV medications: dolutegravir, darunavir and cobicistat in the blood after drug intake has been stopped, in order to understand how long these drugs persist in the blood. The study will specifically look at blood levels of these three drugs after taking them every day for 14 days.
There will be two groups. Participants in Group 1 will take dolutegravir everyday for 14 days, then nothing for 7 days, then dolutegravir and darunavir/cobicistat together for 14 days, nothing for 7 days, and then darunavir/cobicistat alone for 14 days. If participants go into Group 2 they will begin with darunavir/cobicistat everyday for 14 days, then nothing for 7 days, then dolutegravir and darunavir/cobicistat together for 14 days, nothing for 7 days, and then dolutegravir alone for 14 days. Drug levels for both groups will be measured on days 14, 35 and 56. If the participants decide to take part, the duration of the study will be up to 57 days plus a screening visit which will take place up to 28 days prior to the start of the study, and a follow up visit, which takes place 15 to 22 days after the last dose of study medication. Eligible participants will be randomized (1:1 ratio) to group 1 or group 2. Participants and the study doctor will know which study medications the participant is taking at all times during the study.
This is a randomised, cross-over, open label study, which means that the participants will be randomly assigned to the different arms of the study which receive different medications. The participants and the study doctor will know which study medications the participant is taking at all times during the study.This study will be conducted in a single site, in London.
The total duration of the participant's involvement in the study will be up to 57 days plus a screening visit up to 28 days prior to the start of the study, and a follow up visit 27 to 33 days after the last blood measurement.
The participants will be asked to visit the clinic on up to 14 occasions, of which three visits involve staying in the unit for approximately 12 hours (day 14,35 and 56).
Blood samples will be taken from the participants throughout the study to measure the levels of dolutegravir, darunavir and cobicistat in blood. Blood and urine will also be collected throughout the study for safety analysis; this is to ensure the participants are healthy to take part or to continue taking part in the study. The total amount of blood collected from each participant during the study will be approximately 500ml (just below a pint).
Participants will be provided with written information about the study in the form of a participant information sheet and will be allowed adequate time for questions and to consider the study before agreeing to participate. It will be the responsibility of the investigator or the co-investigator to obtain written informed consent prior to undertaking any procedure detailed in the protocol. As part of the consent procedure, participants will also be asked consent to their personal details being entered into TOPS (the over-volunteering protection system).
The investigator or designee will provide adequate explanation of the aims, methods, objectives and potential hazards of the study. They will also be explaining to the participants that they are free to refuse or withdraw from the study for any reason without detriment to their future care or treatment.
A detailed description of each study visit follows below:
Screening visit If the participant agrees to take part, they will firstly be asked to sign the informed consent form and they will be given a copy to keep.
During the visit the following assessments will be carried out:
GP verification of medical history: A medical history questionnaire will be sent to all participants' GPs for verification of medical history. This information will be reviewed by the Investigator as part of the medical history evaluation. If the completed questionnaire is not received from the GP, then the available information regarding the participant will be reviewed by the Investigator. The Investigator will assess this information and decide whether they are sufficiently confident that the inclusion and exclusion criteria are met and whether the participant may be enrolled into the study. This decision must be documented in writing BEFORE the participant is dosed. Copies of sent GP letters and returned confirmation of medical history will be filed in each participant's source documentation.
Baseline Visit, Day 1
Participants will attend the Unit in the morning and will be asked to fast for 8 hours overnight prior to attending. The following evaluations will be performed in the morning of Day 1, before study medication dosing:
Group1:
A Tivicay® (dolutegravir) tablet will be administered with a standard breakfast, made up according to instructions along with 240 ml of water. This will set the nominal time of dosing. Subjects will be instructed to administer Tivicay® at home in the morning on all other days (14 days in total) (with the exception of days 7, and 14, when the drug will be administered in the PK Unit). Participants will be instructed to administer study drugs in the morning within 15 min of standard breakfast.Participants will be given a diet sheet giving examples of a standardised breakfast for them to have at home with the study drug. They will be also reminded to take their study drug to the unit on day 14 as they will take their last dose in the unit on that day.
Group2:
A Rezolsta® (darunavir plus cobicistat) tablet will be administered with a standard breakfast, made up according to instructions along with 240 ml of water. This will set the nominal time of dosing. Subjects will be instructed to administer Rezolsta® at home in the morning on all other days (14 days in total) (with the exception of days 7, and 14, when the drug will be administered in the PK Unit). Subjects will be instructed to administer study drugs in the morning within 15 min of standard breakfast.Participants will be given a diet sheet giving examples of a standardised breakfast for them to have at home with the study drug. They will be also reminded to take their study drug to the unit on day 14 as they will take their last dose in the unit on that day.
From days 15 to 21 and days 36 to 42, participants will be asked to stop taking their study medication for a total of 7 days each time. These are the washout periods. 7) Intensive Pharmacokinetic Visits (Days 14, 35 and 56) Participants will be admitted to the unit in the morning on days 14, 35 and 56 and will remain in the Unit for approximately 12 hours. They will be asked to fast for 8 hours overnight prior to attending.
The following evaluations will be performed in the morning of Days 14, 35 and 56, before study medication dosing: Vital signs (temperature, blood pressure, heart rate, and respiratory rate) • Physical Examination (symptom directed)
Serial blood samples will be taken on 6 occasions over the day (pre-dose (within 10 minutes before dosing), then 2, 4, 6, 8, and 12 hrs later) to measure the levels of study drugs in their blood. A cannula will be placed in a vein in the participant's forearm to allow repeated blood samples to be taken without having to repeatedly use a needle.
The exact time of intake of study medication will be recorded on the CRF. Participants should remain in a semi- recumbent position until four hours post dose.
Patients will be able to leave the unit after the 12 hour sample to return the following morning.
Participants will be required to attend the unit for plasma drug concentration sampling. This will occur at 24 hours post dose.
Participants will attend on days 5, 36 and 57.
Participants will return to the unit on one occasion between days 80 to 90 inclusive and undergo the following evaluations:
Review of AEs
During this visit the following evaluations will be performed:
St Stephens Aids Trust is the lead sponsor of 46 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Women of (WOCBP - definition in Appendix 5) must be using an adequate method of to avoid pregnancy throughout the study and for a period of at least 4 weeks after the study.
A female may be eligible to enter and participate in the study if she:
Men who have partners who are women of childbearing potential (WOCBP - definition in Appendix 5) must be using an adequate method of contraception to avoid pregnancy in their partner throughout the study and for a period of at least 4 weeks after the study (see inclusion criteria 6);
Any contraception method must be used consistently, in accordance with the approved product label and for at least four weeks after discontinuation of IMP.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Tivicay (Dolutegravir 50 mg) for 14 days OD (days 1-14) WASH OUT for 7 days (days 15-21) Tivicay (Dolutegravir 50 mg) OD plus Rezolsta (darunavir/cobicistat 800/150 mg) OD for 14 days (days 22-35) WASH OUT for 7 days (days 36-42) Rezolsta (darunavir/cobicistat 800/150 mg) OD for 14 days (days 43-56)
Drug: Tivicay · Drug: Rezolsta
Rezolsta (darunavir/cobicistat 800/150 mg) OD for 14 days (days 1-14) WASH OUT for 7 days (days 15-21) Tivicay (Dolutegravir 50 mg) OD plus Rezolsta (darunavir/cobicistat 800/150 mg) OD for 14 days (days 22-35) WASH OUT for 7 days (days 36-42) Tivicay (Dolutegravir 50 mg) for 14 days OD (days 43-56)
Drug: Tivicay · Drug: Rezolsta
Assess the pharmacokinetics of dolutegravir and darunavir/cobicistat during co-administration in HIV negative healthy volunteers as measured by Cthrough
Trough concentration (Ctrough) is defined as the concentration at 24 hours after the observed drug dose
Time frame: 8 weeks
Assess the pharmacokinetics of dolutegravir and darunavir/cobicistat during co-administration in HIV negative healthy volunteers as measured by Cmax
Cmax defined as the maximum observed plasma concentration.
Time frame: 8 weeks
Assess the pharmacokinetics of dolutegravir and darunavir/cobicistat during co-administration in HIV negative healthy volunteers as measured by t1/2
t1/2 = Elimination half-life
Time frame: 8 weeks
Assess the pharmacokinetics of dolutegravir and darunavir/cobicistat during co-administration in HIV negative healthy volunteers as measured by Tmax
Tmax = time point at Cmax
Time frame: 8 weeks
Assess the pharmacokinetics of dolutegravir and darunavir/cobicistat during co-administration in HIV negative healthy volunteers as measured by total drug exposure
Total drug exposure is expressed as the area under the plasma concentration-time curve from 0-24 hours after dosing (AUC0-24h)
Time frame: 8 weeks
Assess the safety and tolerability of the studied drugs when co-administered to HIV negative healthy volunteers, assessed by The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
studied drug: Dolutegravir and Darunavir/Cobocistat
Time frame: 10 weeks
investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by Peak plasma concentration (Cmax)
investigate the association between genetic polymorphisms in drug disposition genes and drug exposure
Time frame: 8 weeks
investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by trough concentration (Ctrough)
investigate the association between genetic polymorphisms in drug disposition genes and drug exposure
Time frame: 8 weeks
investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by Area under the plasma concentration versus time curve (AUC)
investigate the association between genetic polymorphisms in drug disposition genes and drug exposure
Time frame: 8 Weeks
Exploratory: the impact of antiretroviral drugs on platelet function
To look at platelet function during antiretroviral intake in HIV negative individuals who take part in clinical trials. Platelet aggregation response as a change in light transmission in a platelet aggregometer, will be measured. The data reported will be the maximal aggregation in response to agonist stimulation
Time frame: 8 weeks
Plan to share: Yes — Only authorised representatives of the sponsor (such as monitors and auditors) and individuals who are authorised on the signature and delegation log will have access to the participants' personal data. This could typically be: doctors, nurses, pharmacists, laboratory staff and data manager within the Trust/Care organisation. It is also possible that the regulatory authorities may wish to access this data. The access given to participants' data is explained in the participant information sheet, so consent will have been given to these individuals outside the care organisation.
No publications or documents are linked to this record.
Ran from Apr 2017 to primary completion in Jan 2018, 8 months.
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This study is completed, as verified in May 2018. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Dolutegravir · Cobicistat mixture with darunavir
St Stephens Aids Trust