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Doravirine, Rifapentine and Isoniazid Interaction (DORIIS)

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ClinicalTrials.gov Identifier: NCT03886701
Recruitment Status : Completed
First Posted : March 22, 2019
Results First Posted : March 3, 2020
Last Update Posted : March 27, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Walter K. Kraft, Thomas Jefferson University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Latent Tuberculosis
Human Immunodeficiency Virus
Rifamycins Causing Adverse Effects in Therapeutic Use
Drug Interaction Potentiation
Interventions Drug: Doravirine (DOR)
Drug: Rifapentine (RPT)
Drug: Isoniazid (INH)
Enrollment 11
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Study Particpants
Hide Arm/Group Description Eleven healthy volunteers enrolled into the study. For period 1 (study days 1-4), participants will be given doravirine 100mg oral tablets dosed twice-daily on study days 1-4. For period 2 (study days 7-21), oral 100mg doravirine will be dosed twice-daily. Weight-based rifapentine and isoniazid (as recommended by the CDC) will be given orally once-weekly on study days 7, 14, and 21.
Period Title: Period 1: Study Days 1-4
Started [1] 11
Completed 11
Not Completed 0
[1]
Healthy volunteers received oral DOR 100 mg twice daily alone
Period Title: Period 2: Study Days 7-21
Started [1] 11
Completed 11
Not Completed 0
[1]
Healthy volunteers received oral DOR 100 mg twice daily together with once weekly RPT and INH
Arm/Group Title Study Particpants
Hide Arm/Group Description Eleven healthy volunteers enrolled into the study.
Overall Number of Baseline Participants 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 11 participants
50
(27 to 56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Female
1
   9.1%
Male
10
  90.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
White
3
  27.3%
Black or African American
8
  72.7%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 11 participants
92.9  (11.3)
1.Primary Outcome
Title Doravirine Maximum Concentration (Cmax)
Hide Description Doravirine maximum observed concentration during the dosing interval
Time Frame Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 1 Period 2
Hide Arm/Group Description:

DOR twice-daily alone (Study days 1-4)

Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.

Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
Overall Number of Participants Analyzed 11 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: ug/mL
1.7
(1.5 to 2)
1.3
(1.1 to 1.5)
2.Primary Outcome
Title Doravirine Area Under the Plasma Concentration Versus Time Curve From 0 to 12 Hours (AUC0-12)
Hide Description Doravirine area under the plasma-concentration time curve derived from plasma sampling during one dosing interval
Time Frame Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 1 Period 2
Hide Arm/Group Description:

DOR twice-daily alone (Study days 1-4)

Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.

Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
Overall Number of Participants Analyzed 11 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr x ug/mL
17.3
(14.9 to 20)
12.3
(10.4 to 14.3)
3.Primary Outcome
Title Doravirine Oral Clearance (CL/F)
Hide Description Doravirine apparent oral clearance derived from plasma sampling
Time Frame Day 4 and 21 (Period 1 and 2): 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 1 Period 2
Hide Arm/Group Description:

DOR twice-daily alone (Study days 1-4)

Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.

Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
Overall Number of Participants Analyzed 11 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/hr
5.9
(24%)
8.4
(26.1%)
4.Secondary Outcome
Title Adverse Event
Hide Description Safety and tolerability
Time Frame Days 1-24 post-dose (period 1 and 2) and 31-34 post-dose (post-study)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 1 Period 2
Hide Arm/Group Description:

DOR twice-daily alone (Study days 1-4)

Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.

Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
Overall Number of Participants Analyzed 11 11
Measure Type: Number
Unit of Measure: participants
Nausea/vomiting 1 0
Dysuria 0 1
Fever 0 1
Headache 0 1
Chills 0 1
Catheter site pain and redness 3 2
Time Frame Daily for the duration of the study and 7-10 days post-study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Period 1 Period 2
Hide Arm/Group Description

DOR twice-daily alone (Study days 1-4)

Doravirine (DOR): Non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV-1 infection in adults in combination with other antiretroviral agents.

Rifapentine (RPT): Rifamycin anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

Isoniazid (INH): Anti-tuberculosis agent indicated for the treatment of latent and active tuberculosis infection.

DOR twice-daily with RPT/INH once-weekly (Study days 7-21)
All-Cause Mortality
Period 1 Period 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/11 (0.00%)   0/11 (0.00%) 
Hide Serious Adverse Events
Period 1 Period 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/11 (0.00%)   0/11 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Period 1 Period 2
Affected / at Risk (%) Affected / at Risk (%)
Total   4/11 (36.36%)   6/11 (54.55%) 
Gastrointestinal disorders     
Nausea/vomiting *  1/11 (9.09%)  0/11 (0.00%) 
General disorders     
Fever *  0/11 (0.00%)  1/11 (9.09%) 
Chills *  0/11 (0.00%)  1/11 (9.09%) 
Catheter site pain and redness *  3/11 (27.27%)  2/11 (18.18%) 
Nervous system disorders     
Headache *  0/11 (0.00%)  1/11 (9.09%) 
Renal and urinary disorders     
Dysuria *  0/11 (0.00%)  1/11 (9.09%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Walter K. Kraft
Organization: Thomas Jefferson University
Phone: 215 955-9077
EMail: walter.kraft@jefferson.edu
Layout table for additonal information
Responsible Party: Walter K. Kraft, Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT03886701    
Other Study ID Numbers: 12690
First Submitted: March 12, 2019
First Posted: March 22, 2019
Results First Submitted: February 13, 2020
Results First Posted: March 3, 2020
Last Update Posted: March 27, 2020