HIV
Conditions
Brief summary
This study is an open-label, prospective pharmacokinetic study investigating two antiretroviral agents in parallel and employing an adaptive design with two stages, whereby the results obtained in the primary stage inform the doses selected for investigation in the secondary stage
Detailed description
The objectives of this study are: Primary * To investigate the pharmacokinetics of a new pharmaceutical formulation of efavirenz (NANO-efavirenz) in HIV negative healthy volunteers after single dose and a steady-state. * To investigate the pharmacokinetics of a new pharmaceutical formulation of lopinavir (NANO-lopinavir) in HIV negative healthy volunteers Secondary * To investigate the safety and tolerability of NANO-efavirenz and NANO-lopinavir in HIV negative healthy volunteers * To assess the bioequivalence of a selected single-dose of NANO-efavirenz to a single dose 600mg of efavirenz as Sustiva® * To investigate the association between genetic polymorphisms in drug disposition genes and drug exposure
Interventions
DRUGKaletra® (lopinavir 400mg/ritonavir 100mg)
BID
DRUG+/- 200mg NANO-Lopinavir
BID
DRUG+/- 200mg ritonavir NORVIR
BID
DRUG200mg NANO-Efavirenz
OD
DRUG50mg NANO-efavirenz
OD
DRUG400mg NANO-Lopinavir
BID
DRUG200mg NANO-Lopinavir
BID
DRUG100mg Ritonavir
BID
DRUG300mg NANO-Efavirenz
OD
DRUG600mg Sustiva
OD
DRUG400mg Sustiva
Sponsors
University of Liverpool
St Stephens Aids Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Volunteers must meet all of the following inclusion criteria within 28 days prior to the baseline visit: 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 65 years, inclusive 4. Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive 5. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 12 weeks 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: * Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications; * Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); * Any 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 7 for an example listing of approved IUDs); * Condom and depot medroxyprogesterone acetate ( DMPA) injections * 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 other method with published data showing that the expected failure rate is \<1% per year. * Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of IP. 6. Willing to consent to their personal details being entered onto the TOPS database 7. Willing to provide proof of identity by photographic ID at screen and any subsequent visit 8. Registered with a GP in the UK
Exclusion criteria
Volunteers who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The pharmacokinetics of a new pharmaceutical formulation of efavirenz (NANOefavirenz) and lopinavir (NANOlopinavir) in HIV negative healthy volunteers, as measured by Ctrough | Assessed from baseline visit (day 1) to : 1) Day 31 (Primary Stage Group A); 2) Day 30 (Primary Stage Group B); 3) Day 80 (Secondary Stage Group A); 4) Day 30 (Secondary Stage Group B) | Trough concentration (Ctrough) is defined as the concentration at 24 hours after the observed drug dose. |
| The pharmacokinetics of a new pharmaceutical formulation of efavirenz (NANOefavirenz) and lopinavir (NANOlopinavir) in HIV negative healthy volunteers, as measured by Cmax | Assessed from baseline visit (day 1) to : 1) Day 31 (Primary Stage Group A); 2) Day 30 (Primary Stage Group B); 3) Day 80 (Secondary Stage Group A); 4) Day 30 (Secondary Stage Group B) | Cmax is defined as the maximum observed plasma concentration |
| The pharmacokinetics of a new pharmaceutical formulation of efavirenz (NANOefavirenz) and lopinavir (NANOlopinavir) in HIV negative healthy volunteers, as measured by t1/2 | Assessed from baseline visit (day 1) to : 1) Day 31 (Primary Stage Group A); 2) Day 30 (Primary Stage Group B); 3) Day 80 (Secondary Stage Group A); 4) Day 30 (Secondary Stage Group B) | t1/2 is defined as the elimination half-life |
| The pharmacokinetics of a new pharmaceutical formulation of efavirenz (NANOefavirenz) and lopinavir (NANOlopinavir) in HIV negative healthy volunteers, as measured by Tmax | Assessed from baseline visit (day 1) to : 1) Day 31 (Primary Stage Group A); 2) Day 30 (Primary Stage Group B); 3) Day 80 (Secondary Stage Group A); 4) Day 30 (Secondary Stage Group B) | Tmax is defined as the time point at Cmax (Tmax) |
| The pharmacokinetics of a new pharmaceutical formulation of efavirenz (NANOefavirenz) and lopinavir (NANOlopinavir) in HIV negative healthy volunteers, as measured by total drug exposure | Assessed from baseline visit (day 1) to : 1) Day 31 (Primary Stage Group A); 2) Day 30 (Primary Stage Group B); 3) Day 80 (Secondary Stage Group A); 4) Day 30 (Secondary Stage Group B) | Total drug exposure will be expressed as the area under the plasma concentration-time curve (AUC): from 0-12 (AUC0-12h) and 0-56 hours (AUC0-56h) for lopinavir; or 0-24 (AUC0-24h) and 0-228 hours (AUC0-24h) for efavirenz. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by Urinalysis | ) From screening visit to day 21 (Primary Stage Group A); 2) From screening visit to day 28 (Primary Stage Group B); 3) From screening visit to day 70 (Secondary Stage Group A); 4) From screening visit to day 28 (Secondary Stage Group B) | Glucose, ketones, blood, pH, proteins, nitrites and leucocytes Pregnancy test for females of childbearing potential (urine) Drug screen |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured haematology | 1) From screening visit to day 45 (Primary Stage Group A); 2) From screening visit to day 44 (Primary Stage Group B); 3) From screening visit to day 94 (Secondary Stage Group A); 4) From screening visit to day 44 (Secondary Stage Group B) | 1. Coulter count with differential 2. Clotting screen; PT, APTT, Fibrinogen |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by clinical chemistry | 1) From screening visit to day 45 (Primary Stage Group A); 2) From screening visit to day 44 (Primary Stage Group B); 3) From screening visit to day 94 (Secondary Stage Group A); 4) From screening visit to day 44 (Secondary Stage Group B) | Serum Biochemistry - Including sodium, potassium, urea, creatinine, total cholesterol and triglycerides, calcium, phosphate, liver enzymes (ALT, AST, GGT), albumin, glucose. |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by concomitant medication check | 1) From screening visit to day 45 (Primary Stage Group A); 2) From screening visit to day 44 (Primary Stage Group B); 3) From screening visit to day 94 (Secondary Stage Group A); 4) From screening visit to day 44 (Secondary Stage Group B) | — |
| Safety and tolerability of NANOefavirenz in HIV negative healthy volunteers, as measured by CNS symptoms questionnaire | 1) Days 2 and 21 (Primary Stage Group A); 2) Days 2, 21, 51, and 70 (Secondary Stage Group A) | — |
| Relationship between genetic polymorphisms and exposure to the studied drugs. | Sample taken at baseline (if consented) | Preliminary comparison between genotype and phenotype |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by Adherence questioning/ pill count | 1) Days 14 and 21 (Primary Stage Group A); 2) Days 7 and 28 (Primary Stage Group B); 3) Days 14, 21, 63, and 70 (Secondary Stage Group A); 4) Days 7 and 28 (Secondary Stage Group B) | — |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by Adverse Events | 1) From screening visit to day 45 (Primary Stage Group A); 2) From screening visit to day 44 (Primary Stage Group B); 3) From screening visit to day 94 (Secondary Stage Group A); 4) From screening visit to day 44 (Secondary Stage Group B) | — |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by symptom directed physical exam | 1) From screening visit to day 45 (Primary Stage Group A); 2) From screening visit to day 44 (Primary Stage Group B); 3) From screening visit to day 94 (Secondary Stage Group A); 4) From screening visit to day 44 (Secondary Stage Group B) | — |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by vital signs | 1) From screening visit to day 45 (Primary Stage Group A); 2) From screening visit to day 44 (Primary Stage Group B); 3) From screening visit to day 94 (Secondary Stage Group A); 4) From screening visit to day 44 (Secondary Stage Group B) | Temperature, blood pressure, heart rate, and respiratory rate |
| Safety and tolerability of NANOefavirenz and NANOlopinavir in HIV negative healthy volunteers, as measured by ECG | 1) From screening visit to day 21 (Primary Stage Group A); 2) From screening visit to day 28 (Primary Stage Group B); 3) From screening visit to day 70 (Secondary Stage Group A); 4) From screening visit to day 28 (Secondary Stage Group B) | 12 lead ECG with calculation of corrected QT interval (Fredericia) |
Countries
United Kingdom
Outcome results
None listed