E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus-1 (Healthy participants) |
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E.1.1.1 | Medical condition in easily understood language |
HIV-1 (Healthy participants) |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020443 |
E.1.2 | Term | Human immunodeficiency virus syndrome |
E.1.2 | System Organ Class | 100000004862 |
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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 is to evaluate the single-dose PK and bioequivalence of DRV 600 mg in the presence of COBI 90 mg when administered as a DRV/COBI FDC tablet dispersed in water compared to the co-administration of the separate available formulations, under fed conditions in healthy participants. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: • To evaluate the single-dose PK and relative bioavailability of COBI 90 mg in the presence of DRV 600 mg when administered as a DRV/COBI FDC tablet compared to co-administration of the separate available formulations, under fed conditions in healthy participants. • To evaluate the short-term safety and tolerability of co-administration of DRV 600 mg and COBI 90 mg, under fed conditions in healthy participants. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each potential participant must satisfy all of the following criteria to be enrolled in the study: 1. 18 to 55 years of age, inclusive. 2. Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. 3. Healthy on the basis of clinical laboratory tests performed at screening. 4. Body weight not less than 50 kg and body mass index (BMI; weight [kg]/height2 [m]2) within the range 18.5 - 30.0 kg/m2 (inclusive). 5. Man or woman (according to their reproductive organs and functions assigned by chromosomal complement). |
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E.4 | Principal exclusion criteria |
Any potential participant who meets any of the following criteria will be excluded from participating in the study: 1. History of or current clinically significant medical illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results. 2. History of malignancy within 5 years before screening. 3. Has one or more laboratory abnormalities at screening or at Day -1. 4. Clinically significant abnormalities during physical examination, vital signs, or 12-lead ECG at screening or at admission to the study site as deemed appropriate by the investigator. 5. Current or chronic history of liver disease. 6. Known hepatic or biliary abnormalities. 7. Known allergies, hypersensitivity, or intolerance to darunavir and/or cobicistat or its excipients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. PK and bioequivalence a. Cmax: The maximum observed plasma analyte concentration b. AUClast: Area under the analyte concentration-time curve (AUC) from time 0 to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation. c. AUC∞: AUC from time 0 to infinite time, calculated as AUClast + Clast/λz, , where Clast is the last observed measurable (non-BQL) concentration; extrapolations of more than 20.00% of the total AUC are reported as approximations. d. Clast: The last observed measurable (non-BQL) plasma analyte concentration. e. λz: Apparent terminal elimination rate constant, determined by linear regression using the terminal log-linear phase of the log-transformed concentration vs time curve. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. PK and relative bioavailability a. Cmax: The maximum observed plasma analyte concentration b. AUClast: Area under the analyte concentration-time curve (AUC) from time 0 to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation. c. AUC∞: AUC from time 0 to infinite time, calculated as AUClast + Clast/λz, , where Clast is the last observed measurable (non-BQL) concentration; extrapolations of more than 20.00% of the total AUC are reported as approximations. d. Clast: The last observed measurable (non-BQL) plasma analyte concentration. e. λz: Apparent terminal elimination rate constant, determined by linear regression using the terminal log-linear phase of the log-transformed concentration vs time curve. 2. Safety and tolerability a. Serious adverse events b. Physical examination c. Clinical laboratory results d. Vital signs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Single-dose, 2-treatment, 2-sequence, 2-period crossover, single-center study |
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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 |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 17 |