| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus (HIV-1) Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| Human Immunodeficiency Virus Infection |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020192 |
| E.1.2 | Term | HIV-1 |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to evaluate the relative bioavailability of two age-appropriate pediatric formulations (tablet and suspension formulation) of EVG co-administered with ritonavir in healthy adult subjects |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary objective of this study is to evaluate the safety of two age-appropriate pediatric formulations (tablet and suspension formulation) of EVG co-administered with ritonavir in healthy adult subjects |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria (as applicable) to be eligible for participation in this study.
1. Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.
2. Must be between 18 and 45 years of age, inclusive.
3. Must be a nonsmoker. The use of nicotine or nicotine-containing products must be discontinued 90 days prior to the first dose of study drug.
4. Must have a calculated body mass index (BMI) from 19 ≤ BMI ≤ 30 kg/m2 at study screening.
5. Must be HIV-1 antibody negative.
6. Must be hepatitis B (HBV) surface antigen negative.
7. Must be hepatitis C (HCV) antibody negative.
8. Have an estimated creatinine clearance (CLCr) ≥ 90 mL/min (using the Cockcroft-Gault method)
9. Females of childbearing potential (as defined in Section 7.9.1) must have a negative serum pregnancy test.
10. Females of childbearing potential must agree to utilize protocol recommended highly effective contraception methods from 3 weeks prior to baseline (Day -1) throughout the duration of study treatment and for 30 days following the last dose of study drug.
11. Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least 3 months prior to study dosing.
12. Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product.
13. Male subjects must refrain from sperm donation from Day -1 through completion of the study and continuing for at least 30 days from the date of last dose of study drug.
14. Subjects must refrain from blood donation from Day -1 through completion of the study and continuing for at least 30 days from date of last dose of study drug.
15. Must, in the opinion of the Investigator, be in good health based upon medical history, physical examination (including vital signs), and screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory’s reference ranges unless the results have been determined by the Investigator to have no clinical significance.
16. Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the Investigator in consultation with the Sponsor. Subjects must have PR between 120 – 210 msec, and QTcF of <450 for males and <470 for females.
17. Must be willing and able to comply with all study requirements. |
|
| E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria (as applicable) are not to be enrolled in this study.
1. Pregnant or lactating subjects.
2. Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with subject treatment, assessment, or compliance with the protocol.
3. Have previously participated in an investigational trial involving administration of any investigational compound within 30 days prior to the study dosing.
4. Current alcohol or substance abuse judged by the Investigator to potentially interfere with subject compliance.
5. Have poor venous access and are unable to donate blood.
6. Have donated blood within 56 days of study dosing.
7. Have donated plasma within 7 days of study dosing.
8. Have taken any prescription medications or over-the-counter medications including herbal products within 28 days of commencing study drug dosing with the exception of vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications.
9. Have history of significant drug sensitivity or drug allergy. disorders, active infection, or malignancy that are clinically significant or requiring treatment.
10. Known hypersensitivity to the study drugs, the metabolites or formulation excipients
11. Have been treated with systemic steroids, immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies).
12. Have a history or family history of Long QT Syndrome, Wolfe-Parkinson-White Syndrome, or have a family history of sudden cardiac death or unexplained death in an otherwise healthy individual between the ages of 1 and 40 years.
13. History of syncope, palpitations, or unexplained dizziness.
14. Have an implanted defibrillator or pacemaker.
15. Have a history of liver disease, including Gilbert’s Disease.
16. Are unable to comply with study requirements.
17. Believed, by the study Investigator, to be inappropriate for study participation for any reason. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoints were the PK parameters AUClast, AUCinf, and Cmax for EVG. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At screening, baseline (Day -1), and at various time points during the study |
|
| E.5.2 | Secondary end point(s) |
| The secondary endpoints were %AUCexp, Tmax, Clast, Tlast, λz, and t1/2 of EVG in Cohort 1 and Cohort 2, AUClast, AUCinf, and Cmax of RTV in Cohort 1 and Cohort 2, AUCtau, Ctau, and Cmax of EVG and RTV in Cohort 3, and the incidences of AEs and laboratory abnormalities. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| At screening, baseline (Day -1), and at various time points during the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | Yes |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| The comparator is EVG Adult formulation against EVG pediatric formulation |
|
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
| E.8.4 | Will this trial be conducted at multiple sites globally? | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 23 |
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