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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001213-27 | EudraCT Number | ||
| TMC114FD2HTX1002 | Other Identifier | Janssen Sciences Ireland UC |
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The purpose of this study is to evaluate the pharmacokinetics and relative bioavailability of Emtricitabine (FTC) and Tenofovir alafenamide (TAF) when administered as a fixed-dose combination (FDC) with darunavir (DRV) and cobicistat (COBI) (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) relative to administration as an FDC with Elvitegravir (EVG) and COBI (Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide), under fed conditions in healthy subjects (Panel 1); evaluate the single-dose pharmacokinetics and relative bioavailability of DRV, COBI, FTC and TAF when administered as an FDC (D/C/F/TAF) or as separate agents (D+C+FTC/TAF), under fed conditions in healthy subjects (Panel 2) and to evaluate the impact of food (fasting or high-fat breakfast) on the single-dose pharmacokinetics of DRV, COBI, FTC, and TAF when administered as an FDC (D/C/F/TAF) in healthy subjects (Panel 3).
This is a Phase 1, 3-panel, open-label, randomized, 2-way crossover study in healthy subjects. Healthy subjects will be divided over 3 panels (Panel 1, 2 and 3). Subjects will be randomized within each panel. In each panel, during 2 subsequent sessions, each subject will receive 2 treatments (Treatments A and B in Panel 1, Treatments C and D in Panel 2, and Treatments E and F in Panel 3). Each treatment is defined as follows: Treatment A: single oral dose of D/C/F/TAF 800/150/200/10 milligram (mg) as FDC tablet under fed conditions (standardized regular breakfast); Treatment B: single oral dose of E/C/F/TAF 150/150/200/10 mg as FDC tablet under fed conditions; Treatment C: single oral dose of D/C/F/TAF 800/150/200/10 mg as FDC tablet under fed conditions; Treatment D: single oral dose of DRV as 800-mg tablet, FTC/TAF as 200/10 mg tablet and COBI 150 mg tablet under fed conditions. Treatment E: single oral dose of D/C/F/TAF 800/150/200/10 mg as FDC tablet, under fasted condition and Treatment F: single oral dose of D/C/F/TAF 800/150/200/10 mg tablet, with a standardized high-fat breakfast. Each treatment will be separated by a washout period of at least 7 days. Primarily pharmacokinetic parameters will be assessed. Subjects' safety will be assessed throughout.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Panel 1: Group 1 | Experimental | Subject will receive a single oral tablet of fixed dose combination (FDC) containing darunavir (DRV)/ cobicistat (COBI)/emtricitabine (FTC) /tenofovir alafenamide (TAF) (D/C/F/TAF) under fed conditions (standardized regular breakfast, test Panel 1) on Day 1 of treatment period 1 and by FDC of elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/ tenofovir alafenamide (TAF) (E/C/F/TAF) under fed conditions (standardized regular breakfast, reference Panel 1) on Day 1 of treatment period 2. |
|
| Panel 1: Group 2 | Experimental | Subject will receive a single oral tablet of FDC containing E/C/F/TAF under fed conditions (standardized regular breakfast, reference Panel 1) on Day 1 of treatment period 1 and a single oral tablet of FDC containing D/C/F/TAF under fed conditions (standardized regular breakfast, test Panel 1) on Day 1 of treatment period 2. |
|
| Panel 2: Group 1 | Experimental | Subject will receive a single oral tablet of D/C/F/TAF under fed conditions (standardized regular breakfast, test Panel 2) on Day 1 of treatment period 1 and a single oral tablet of DRV, a tablet of emtricitabine/ tenofovir alafenamide (FTC/TAF) and a tablet of COBI under fed conditions (standardized regular breakfast, reference Panel 2) on Day 1 of treatment period 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Darunavir/Cobicistat/Emtricitabine/Tenofovir alafenamide FDC | Drug | A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | The Cmax is the maximum observed plasma concentration. | Up to 72 Hours after study drug administration |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time. | Up to 72 Hours after study drug administration |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant. | Up to 72 Hours after study drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects with Adverse Events | An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | From signing the Informed Consent Form (ICF) up to 10 days after last study drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | The Tmax is defined as actual sampling time to reach maximum observed analyte concentration. | Up to 72 Hours after study drug administration |
| Plasma Concentration at the Last Quantifiable Time Point (Clast) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Sciences Ireland UC Clinical Trials | Janssen Sciences Ireland UC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Antwerp | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30412360 | Derived | Crauwels HM, Baugh B, Van Landuyt E, Vanveggel S, Hijzen A, Opsomer M. Bioequivalence of the Once-Daily Single-Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability. Clin Pharmacol Drug Dev. 2019 May;8(4):480-491. doi: 10.1002/cpdd.628. Epub 2018 Nov 9. |
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| Panel 2: Group 2 | Experimental | Subject will receive a single oral tablet of DRV, a tablet of FTC/TAF and a tablet of COBI under fed conditions (standardized regular breakfast, reference Panel 2) on Day 1 of treatment period 2 and a single oral tablet of D/C/F/TAF under fed conditions (standardized regular breakfast, test Panel 2) on Day 1 of treatment period 2. |
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| Panel 3: Group 1 | Experimental | Subject will receive a single oral tablet of D/C/F/TAF under fasted conditions (test Panel 3) on Day 1 of treatment period 1 and a single oral tablet of D/C/F/TAF with a standardized high-fat breakfast (reference Panel 3) on Day 1 of treatment period 2. |
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| Panel 3: Group 2 | Experimental | Subject will receive a single oral tablet of D/C/F/TAF with a standardized high-fat breakfast (reference Panel 3) on Day 1 of treatment period 1 followed by a single oral tablet of D/C/F/TAF under fasted conditions (test Panel 3) on Day 1 of treatment period 2. |
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| Elvitegravir /Cobicistat/Emtricitabine/Tenofovir alafenamide FDC | Drug | A tablet containing EVG 150 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg as FDC will be administered. |
|
| Darunavir | Drug | A tablet containing Darunavir (DRV) 800 mg will be administered. |
|
| Emtricitabine/Tenofovir alafenamide (FTC/TAF) | Drug | A tablet containing Emtricitabine (FTC) 200 mg and Tenofovir alafenamide (TAF) 10 mg will be administered. |
|
| Cobicistat | Drug | A tablet containing cobicistat (COBI) 150 mg will be administered. |
|
| High-fat Breakfast | Other | High-fat breakfast will be administered. |
|
| Standardized Regular Breakfast | Other | Standardized regular breakfast will administered. |
|
The Clast is the last observed quantifiable plasma concentration above the quantification limit. |
| Up to 72 Hours after study drug administration |
| Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log linear phase of the drug concentration-time curve. | Up to 72 Hours after study drug administration |
| Elimination Half-Life (t1/2) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z). | Up to 72 Hours after study drug administration |
| Time to Last Quantifiable Plasma Concentration (Tlast) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | The Tlast is the time to last observed quantifiable plasma concentration. | Up to 72 Hours after study drug administration |
| Ratio of AUClast of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | Ratio of individual AUClast values between test and reference treatment will be observed. For Panel 1, test will be treatment A and reference will be treatment B, for Panel 2, test will be treatment C and reference will be treatment D and for Panel 3, test will be treatment D and reference will be treatment F. | Up to 72 Hours after study drug administration |
| Ratio of AUC[0-infinity] of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) | Ratio of individual AUC[0-infinity] values between test and reference treatment will be observed. For Panel 1, test will be treatment A and reference will be treatment B, for Panel 2, test will be treatment C and reference will be treatment D and for Panel 3, test will be treatment D and reference will be treatment F. | Up to 72 Hours after study drug administration |
| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069454 | Darunavir |
| C509700 | elvitegravir |
| D000069547 | Cobicistat |
| D000068679 | Emtricitabine |
| C442442 | tenofovir alafenamide |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D002219 | Carbamates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D005663 | Furans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013844 | Thiazoles |
| D001393 | Azoles |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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