HIV Clinical Trial
— RIFTOfficial title:
The Effect of Rifampicin on the Plasma Pharmacokinetics of Emtricitabine (FTC) and Tenofovir Alafenamide Fumarate (TAF) and Intracellular Tenofovir-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP)
Verified date | February 2018 |
Source | St Stephens Aids Trust |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to look at the levels of three HIV medications: Descovy®,
Viread® and Rifadin® 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 28 days. Participants will take Descovy®
on a first stage, a combination of Descovy® and Rifadin® on a second stage, and Viread® on a
third stage. If the participants decide to take part, the duration of the study will be up to
85 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 28 to 36 days after the last dose of study
medication. This study is not randomised which means that all participants will receive all
study medications in the same order. The participant and the study doctor will know which
study medications the participant is taking at all times during the study.
During the study, numerous blood samples will be taken which could cause inconvenience and
distress for patients. Every effort will be made by study staff to minimise this. There are a
lot of clinic visits during the study and three full days in the unit which may inconvenience
patients. However, participants will be made aware of this both verbally and in the patient
information sheet. Participants will also receive compensation for their time and travel
expenses whilst participating in the trial. Participants or participants' partners who plan
to become pregnant during the study will not be allowed to take part in the study. Further to
this (if applicable), participants must use effective contraception for the duration of the
study. Participants will have to adhere to other restrictions as detailed in the participant
information sheet. These restrictions will be explained in full to all participants.
Status | Completed |
Enrollment | 21 |
Est. completion date | January 10, 2018 |
Est. primary completion date | January 10, 2018 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility |
Inclusion Criteria: 1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements 2. Male or non-pregnant, non-lactating females. 3. Between 18 to 60 years, inclusive 4. Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive (with weight =50kg). 5. ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat is allowed for eligibility determination. 6. Women of childbearing potential (WOCBP - definition in Appendix 4) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 3 months after the study. A female may be eligible to enter and participate in the study if she: 1. is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and = 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, 2. is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy: 3. Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications; (when this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception]. 4. Any non-hormonal intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see protocol appendix 4 for an example listing of approved IUDs); 5. Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject; Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of IP. 7. Men who have partners who are women of childbearing potential (WOCBP - definition in Appendix 4 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); True abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications (When this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception]. Any non-hormonal intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see Appendix 4 for an example listing of approved IUDs); Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject; Any contraception method must be used consistently, in accordance with the approved product label and for at least four weeks after discontinuation of IMP. 8. Willing to consent to their personal details being entered onto the TOPS database 9. Willing to provide proof of identity by photographic ID at screen and any subsequent visit 10. Registered with a GP in the UK Exclusion Criteria: 1. Any clinically significant acute or chronic medical illness 2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations 3. Positive blood screen for hepatitis B surface antigen or C antibody 4. Positive blood screen for HIV-1 or 2 by antibody/antigen assay 5. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) 6. History or presence of allergy to the study drugs and their components: tenofovir alafenamide fumarate, tenofovir disoproxil fumarate, emtricitabine or excipients, croscarmellose sodium, lactose monohydrate magnesium stearate (E572), microcrystalline cellulose (E460), starch pregelatinised, glycerol triacetate (E1518), hypromellose (E464), indigo carmine aluminium lake (E132), lactose monohydrate, titanium dioxide (E171), polyvinyl alcohol, macrogol 3350, talc, corn starch, magnesium stearate. 7. Current or recent (within three months) gastrointestinal disease 8. Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study 9. Exposure to any investigational drug (or placebo) or participation in a clinical study involving the donation of blood samples within three months of first dose of study drug 10. Use of any other drugs (unless approved by the Investigator), including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs. 11. Females of childbearing potential without the use of effective birth control methods, or not willing to continue practising these birth control methods for at least 4 weeks after the end of the treatment period. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Chelsea and Westminster Hospital NHS Foundation Trust | London |
Lead Sponsor | Collaborator |
---|---|
St. Stephens Clinical Research |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by Ctrough. | Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, in HIV negative healthy volunteers, as measured by Ctrough. Trough concentration (Ctrough) is defined as the concentration at 24 hours after the observed drug dose. | 12 Weeks | |
Primary | Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by Cmax. | Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin in HIV negative healthy volunteers, as measured by Cmax. Cmax is defined as the maximum observed plasma concentration. | 12 weeks | |
Primary | Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by t1/2 | Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin in HIV negative healthy volunteers, as measured by t1/2. t1/2 = Elimination half-life | 12 weeks | |
Primary | Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by Tmax | Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin in HIV negative healthy volunteers, as measured by Tmax. Tmax = time point at Cmax | 12 weeks | |
Primary | Assess the pharmacokinetics of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin, as measured by total drug exposure | Assess the pharmacokinetics of TAF, plasma tenofovir, intracellular tenofovir-diphosphate (TFV-DP), FTC, and emtricitabine tri-phosphate (FTC-TP), during administration of TAF/FTC and TDF alone and during co-administration of TAF/FTC with rifampicin 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) | 12 weeks | |
Secondary | 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: Descovy, Descovy/Rifadin, Viread. | 12 Weeks | |
Secondary | Exploratory: 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 | 12 Weeks | |
Secondary | Exploratory: 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 | 12 Weeks | |
Secondary | Exploratory: Investigate the association between genetic polymorphisms in drug disposition genes and drug exposure as measured by by Area under the plasma concentration versus time curve (AUC) | Investigate the association between genetic polymorphisms in drug disposition genes and drug exposure | 12 Weeks | |
Secondary | 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 | 12 Weeks |
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