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Study to Evaluate Pharmacokinetics, Safety and Tolerability of Dolutegravir and Rilpivirine (JULUCA™) 50 Milligram (mg)/25 mg Tablets in Healthy Subjects of Japanese Descent

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ClinicalTrials.gov Identifier: NCT03984838
Recruitment Status : Not yet recruiting
First Posted : June 13, 2019
Last Update Posted : June 13, 2019
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
ViiV Healthcare

Brief 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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: JULUCA (Dolutegravir and Rilpivirine) 50mg/25mg FDC tablet Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of Dolutegravir + Rilpivirine (JULUCA™) 50 mg/25 mg Tablets in Healthy Participants of Japanese Descent
Estimated Study Start Date : June 14, 2019
Estimated Primary Completion Date : August 19, 2019
Estimated Study Completion Date : August 19, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Subjects receiving Dolutegravir and Rilpivirine FDC
Subjects will receive Dolutegravir/Rilpivirine 50mg/25mg fixed dose combination (FDC) tablet as a single oral dose in a fed state.
Drug: JULUCA (Dolutegravir and Rilpivirine) 50mg/25mg FDC tablet
JULUCA tablets will be administered orally once daily with a meal. It will be available as a fixed dose combination of Dolutegravir 50mg and Rilpivirine 25mg.




Primary Outcome Measures :
  1. Area under the concentration (AUC) from time zero extrapolated to infinite time (AUC [0-infinity]) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of AUC(0-infinity).

  2. Area under the concentration time curve from time zero to last time of quantifiable concentration (AUC [0-t]) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of AUC(0-t).

  3. Maximum observed plasma concentration (Cmax) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of Cmax.

  4. Absorption lag time (tlag) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of tlag.

  5. Time to reach maximum observed concentration (tmax) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of tmax.

  6. Time of last quantifiable concentration (t) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of time of last quantifiable concentration (t).

  7. The elimination half-life (t1/2) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of t1/2.

  8. Apparent elimination rate constant (Lambdaz) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of apparent elimination rate constant (Lambdaz).

  9. Percentage of AUC(0-infinity) that was extrapolated (%AUCex) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of %AUCex.

  10. Area under the plasma concentration time curve from time zero to 24 hours (AUC[0-24]) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of AUC(0-24).

  11. Area under the plasma concentration time curve from time zero to 72 hours (AUC[0-72]) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of AUC(0-72).

  12. Apparent oral clearance (CL/F) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of CL/F.

  13. Apparent oral volume of distribution (Vz/F) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of Vz/F.

  14. Last quantifiable concentration (Ct) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of Ct.

  15. Concentration at 24-hour post-dose (C24) following a single oral dose of DTG/RPV 50 mg/25 mg FDC [ Time Frame: For DTG PK analysis up to Day 6; For RPV PK analysis up to Day 12 ]
    Blood samples will be collected for analysis of C24.


Secondary Outcome Measures :
  1. Number of subjects with any adverse event (AE) and serious adverse events (SAE) [ Time Frame: Up to Day 18 ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening; which requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgment.

  2. Change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  3. Absolute values of neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  4. Change from Baseline in hemoglobin level [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  5. Absolute values of hemoglobin level [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  6. Change from Baseline in hematocrit level [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  7. Absolute values of hematocrit level [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  8. Change from Baseline in red blood cell (RBC) count [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  9. Absolute values of RBC count [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  10. Change from Baseline in mean corpuscular hemoglobin (MCH) [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  11. Absolute values of MCH [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  12. Change from Baseline in mean corpuscular volume (MCV) [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  13. Absolute values of MCV [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  14. Change from Baseline in percent reticulocytes [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  15. Absolute values of percent reticulocytes [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of hematology parameters.

  16. Change from Baseline in blood urea nitrogen (BUN), glucose, calcium, total and direct bilirubin, creatinine and total protein levels [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  17. Absolute values of blood urea nitrogen (BUN), glucose, calcium, total and direct bilirubin, creatinine and total protein levels [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  18. Change from Baseline in sodium and potassium levels [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  19. Absolute values of sodium and potassium levels [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  20. Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  21. Absolute values of AST, ALT and alkaline phosphatase levels [ Time Frame: Baseline and Day 3 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  22. Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Baseline and Follow-up (Up to Day 18) ]
    SBP and DBP will be assessed in the supine position with a completely automated device.

  23. Absolute values of SBP and DBP [ Time Frame: Baseline and Follow-up (Up to Day 18) ]
    SBP and DBP will be assessed in the supine position with a completely automated device.

  24. Change from Baseline in pulse rate [ Time Frame: Baseline and Follow-up (Up to Day 18) ]
    Pulse measurements will be assessed in the supine position with a completely automated device.

  25. Absolute values of pulse rate [ Time Frame: Baseline and Follow-up (Up to Day 18) ]
    Pulse measurements will be assessed in the supine position with a completely automated device.

  26. Change from Baseline in body temperature [ Time Frame: Baseline and Follow-up (Up to Day 18) ]
    Changes in body temperature from Baseline will be assessed.

  27. Absolute values of body temperature [ Time Frame: Baseline and Follow-up (Up to Day 18) ]
    Changes in body temperature from Baseline will be assessed.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 <35%)
  • Subjects with current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Subjects with QTcF >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 <=2 grams per day, is allowed for use any time during the study
  • Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
  • Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research
  • Subjects with presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention
  • Subjects with positive Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention (Note: Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained)
  • Subjects with positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention (Note: Test is optional and subjects with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing)
  • Subjects with positive pre-study drug or alcohol screen
  • Subjects with positive human immunodeficiency virus (HIV) antibody test
  • Subjects with regular use of known drugs of abuse
  • Subjects with creatinine clearance (CrCL) <60 milliliter per minute
  • Employment with Janssen, ViiV, GlaxoSmithKline(GSK), or with the Investigator or study site, with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, as well as family members of the employees or the Investigator
  • Subjects with urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening
  • Subjects with regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03984838


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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United States, California
GSK Investigational Site Not yet recruiting
Glendale, California, United States, 91206
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 89904466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
ViiV Healthcare
Janssen, LP
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare

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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT03984838     History of Changes
Other Study ID Numbers: 212312
First Posted: June 13, 2019    Key Record Dates
Last Update Posted: June 13, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ViiV Healthcare:
Dolutegravir, Rilpivirine, HIV infection, Fixed-dose combination, Japanese, Pharmacokinetics

Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Dolutegravir
Rilpivirine
Dolutegravir, rilpivirine drug combination
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors