Phase 1
Completed N=16
Study to Evaluate Pharmacokinetics, Safety and Tolerability of Dolutegravir and Rilpivirine (JULUCA™) 50 Milligram (mg)/25 mg Tablets in Healthy Subjects of Japanese Descent
Source: ClinicalTrials.gov NCT03984838 ↗Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Jul 2020
Primary outcomePrimary: Area Under the Concentration (AUC) Time Curve From Time Zero Extrapolated to Infinite Time (AUC [0-infinity]) of DTG — 90.9402 Hours*micrograms per milliliter
Summary
Dolutegravir (DTG), a human immunodeficiency virus (HIV)-1 integrase inhibitor (INI), and Rilpivirine (RPV), a non-nucleoside HIV-1 reverse transcriptase inhibitor (NNRTI), are each approved in the United States (US), European Union, and other countries for the treatment of HIV-1 infection. JULUCA is a combination of Dolutegravir and Rilpivirine indicated for the treatment of HIV-1 infection in antiretroviral (ARV) experienced adult subjects who are switching from their current antiretroviral treatment to the 2-drug combination. Although, the pharmacokinetics (PK), safety and tolerability of DTG/RPV (50 milligram [mg]/25mg) fixed-dose combination (FDC) tablets have been extensively studied, these parameters have not been assessed exclusively in Japanese subjects. This study will evaluate the pharmacokinetics, safety and tolerability of a single dose DTG/RPV 50 mg/25 mg FDC in a healthy adult Japanese population to support a post-approval commitment for DTG/RPV 50 mg/25 mg FDC in Japan.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration (AUC) Time Curve From Time Zero Extrapolated to Infinite Time (AUC [0-infinity]) of DTG |
90.9402 | — |
| PRIMARY AUC (0-infinity) of RPV |
4027.9415 | — |
| PRIMARY Area Under the Concentration Time Curve From Time Zero to Last Time of Quantifiable Concentration (AUC [0-t]) of DTG |
89.1993 | — |
| PRIMARY AUC (0-t) of RPV |
3920.9404 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of DTG |
4108.5 | — |
| PRIMARY Cmax of RPV |
136.10 | — |
| PRIMARY Absorption Lag Time (Tlag) of DTG |
0.0 | — |
| PRIMARY Tlag of RPV |
0.5 | — |
| PRIMARY Time to Reach Maximum Observed Concentration (Tmax) of DTG |
3.0085 | — |
| PRIMARY Tmax of RPV |
4.4976 | — |
| PRIMARY Time of Last Quantifiable Concentration (Tlast) of DTG |
120.0854 | — |
| PRIMARY Tlast of RPV |
214.5819 | — |
| PRIMARY Elimination Half-life (t1/2) of DTG |
17.3135 | — |
| PRIMARY T1/2 of RPV |
37.2571 | — |
| PRIMARY Apparent Elimination Rate Constant (Lambda z) of DTG |
0.0405 | — |
| PRIMARY Lambda z of RPV |
0.0196 | — |
| PRIMARY Percentage of AUC(0-infinity) That Was Extrapolated (%AUCex) of DTG |
1.9065 | — |
| PRIMARY Percentage AUCex of RPV |
2.6501 | — |
| PRIMARY Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) of DTG |
54.9466 | — |
| PRIMARY AUC (0-24) of RPV |
1420.2525 | — |
| PRIMARY Area Under the Plasma Concentration Time Curve From Time Zero to 72 Hours (AUC[0-72]) of DTG |
85.3534 | — |
| PRIMARY AUC (0-72) of RPV |
2886.6035 | — |
| PRIMARY Apparent Oral Clearance (CL/F) of DTG |
0.5498 | — |
| PRIMARY CL/F of RPV |
6.2066 | — |
| PRIMARY Apparent Oral Volume of Distribution (Vz/F) of DTG |
14.0079 | — |
| PRIMARY Vz/F of RPV |
347.3276 | — |
| PRIMARY Last Quantifiable Concentration (Ct) of DTG |
54.59 | — |
| PRIMARY Ct of RPV |
1.836 | — |
| PRIMARY Concentration at 24-hour Post-dose (C24) of DTG |
1453.6 | — |
| PRIMARY C24 of RPV |
43.35 | — |
| SECONDARY Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) |
2; 0 | — |
| SECONDARY Change From Baseline in Neutrophil, Lymphocyte, Leukocyte, Monocyte, Eosinophil, Basophil and Platelet Count |
-0.03; -0.04; -0.16; -0.03; -0.04; 5.4 | — |
| SECONDARY Absolute Values of Neutrophil, Lymphocyte, Leukocyte, Monocyte, Eosinophil, Basophil and Platelet Count |
0.04; 0.01; 0.20; 0.16; 5.76; 5.59 | — |
| SECONDARY Change From Baseline in Hemoglobin Level |
10.1 | — |
| SECONDARY Absolute Values of Hemoglobin Level |
140.9; 151.0 | — |
| SECONDARY Change From Baseline in Hematocrit Level |
0.0308 | — |
| SECONDARY Absolute Values of Hematocrit Level |
0.4248; 0.4556 | — |
| SECONDARY Change From Baseline in Erythrocytes |
0.358 | — |
| SECONDARY Absolute Values of Erythrocytes |
4.688; 5.046 | — |
| SECONDARY Change From Baseline in Mean Corpuscular Hemoglobin (MCH) |
-0.10 | — |
| SECONDARY Absolute Values of MCH |
30.04; 29.94 | — |
| SECONDARY Change From Baseline in Mean Corpuscular Volume (MCV) |
-0.43 | — |
| SECONDARY Absolute Values of MCV |
90.87; 90.44 | — |
| SECONDARY Change From Baseline in Reticulocytes |
0.13 | — |
| SECONDARY Absolute Values of Reticulocytes |
1.47; 1.59 | — |
| SECONDARY Change From Baseline in Blood Urea Nitrogen (BUN), Glucose, Calcium, Sodium, and Potassium Levels |
0.0483; -0.1908; 0.02; 2.8; 0.2901 | — |
| SECONDARY Absolute Values of BUN, Glucose, Calcium, Sodium, and Potassium Levels |
2.3079; 2.3562; 5.5163; 5.3255; 4.18; 4.19 | — |
| SECONDARY Change From Baseline in Total and Direct Bilirubin, Creatinine and Protein Levels |
3.954; 0.428; 2.7072; 4.2 | — |
| SECONDARY Absolute Values of Total and Direct Bilirubin, Creatinine and Protein Levels |
11.008; 14.963; 2.565; 2.993; 80.3335; 83.0408 | — |
| SECONDARY Change From Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Levels |
3.2; 0.6; 0.9 | — |
| SECONDARY Absolute Values of AST, ALT and ALP Levels |
19.4; 22.6; 17.9; 18.5; 52.3; 53.1 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
6.2; 1.6 | — |
| SECONDARY Absolute Values of SBP and DBP |
107.0; 113.2; 70.1; 71.7 | — |
| SECONDARY Change From Baseline in Pulse Rate |
8.7 | — |
| SECONDARY Absolute Values of Pulse Rate |
58.0; 66.7 | — |
| SECONDARY Change From Baseline in Body Temperature |
0.06 | — |
| SECONDARY Absolute Values of Body Temperature |
36.16; 36.21 | — |
Eligibility Criteria
Inclusion Criteria
- Subject must be 18 to 55 years of age, at the time of signing the informed consent
- Subjects who were born in Japan with 4 ethnic Japanese grandparents. Subjects who have not lived outside Japan for more than 10 years and who are Japanese passport holders (current or expired)
- Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and electrocardiogram [ECG])
- Subjects with body weight >=50 kilogram (kg) (110 pounds) for men and >=45kg (99 pounds) for women and body mass index (BMI) within the range 18.5-31.0 kg per square meter (kg/m^2)
- Male or female subjects; Male subjects with no specific restrictions
- A female subject is eligible to participate if she is not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP)
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
- Subjects capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
Exclusion Criteria
- Subjects with history of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data
- Subjects with abnormal blood pressure (as determined by the investigator)
- Subjects with alanine transaminase (ALT) >1.5 times upper limit of normal (ULN)
- Subjects with bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 460 millisecond (msec)(Based on the average of the 12-Lead-electrocardiogram (ECG) triplicate readings obtained at Screening) (Note: The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial)
- Subjects with past or intended use of over-the-counter or prescription medication including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing. Acetaminophen, at doses of 14 units for males or >7 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240mL) of beer, 1 glass (125mL) of wine or 1 (25mL) measure of spirits
- Subjects with sensitivity to heparin or heparin-induced thrombocytopenia
- Subjects with sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study
Data sourced from ClinicalTrials.gov (NCT03984838). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.