Interaction With HIV Antiretroviral Agents

Study Overview
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Brief Summary
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To investigate the pharmacokinetic drug-drug interaction potential of fixed dose antiretroviral therapies, i.e. ATRIPLA, COMPLERA, STRIBILD, TRIUMEQ, or any approved antiretroviral protease inhibitor in combination with (preferably) TRIUMEQ, on the exposure to riociguat in HIV patients on a stable dose of one of these therapies. • To Assess the safety and tolerability of riociguat treatment in combination with these fixed-dose antiretroviral therapies.

Official Title
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Potential Pharmacokinetic Interaction of Human Immunodeficiency Virus (HIV) Antiretroviral Agents as Fixed-dose Combinations and Riociguat in HIV Patients

Conditions
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HIV-DDI

Intervention / Treatment
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* Drug: Riociguat (Adempas, BAY 63-2521)
* Drug: ATRIPLA
* Drug: COMPLERA
* Drug: STRIBILD
* Drug: TRIUMEQ
* Drug: Antiretroviral protease inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged >=18 to <65 years with a confirmed diagnosis of HIV receiving a stable regimen of ATRIPLA, COMPLERA, STRIBILD, TRIUMEQ, or any approved antiretroviral protease inhibitor such as atazanavir, darunavir, indinavir, ritonavir, and saquinavir in combination with (preferably) TRIUMEQ consistent with the most recent prescribing information documents for at least 6 weeks before concomitant administration of a single oral dose of 0.5 mg riociguat No clinical evidence of pulmonary hypertension Written informed consent Exclusion Criteria: Severe diseases for which it can be assumed that the pharmacokinetics or effects of the study drug will not be normal History of coronary artery disease Symptomatic postural hypotension (e.g. dizziness, lightheadedness) History of bronchial asthma or any other airway disease Renal impairment with creatinine clearance <15 mL/min Severe hepatic impairment (Child-Pugh class C) Systolic blood pressure below 100 mmHg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Riociguat and ATRIPLA<br> | Drug: Riociguat (Adempas, BAY 63-2521)<br>* 0.5 mg, Oral (fasted conditions), 1 single dose<br>Drug: ATRIPLA<br>* 600 mg efavirenz, 200 mg emtricitabine, and 300 mg tenofovir disoproxil fumarate, i.e. 1 tablet, once daily<br>|
| Experimental: Riociguat and COMPLERA<br> | Drug: Riociguat (Adempas, BAY 63-2521)<br>* 0.5 mg, Oral (fasted conditions), 1 single dose<br>Drug: COMPLERA<br>* 200 mg emtricitabine, 25 mg rilpivirine, and 300 mg tenofovir disoproxil fumarate, i.e. 1 tablet, once daily<br>|
| Experimental: Riociguat and STRIBILD<br> | Drug: Riociguat (Adempas, BAY 63-2521)<br>* 0.5 mg, Oral (fasted conditions), 1 single dose<br>Drug: STRIBILD<br>* 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 300 mg tenofovir disoproxil fumarate, i.e. 1 tablet, once daily<br>|
| Experimental: Riociguat and TRIUMEQ<br> | Drug: Riociguat (Adempas, BAY 63-2521)<br>* 0.5 mg, Oral (fasted conditions), 1 single dose<br>Drug: TRIUMEQ<br>* 600 mg abacavir, 50 mg dolutegravir, and 300 mg lamivudine, i.e. 1 tablet, once daily<br>|
| Experimental: Riociguat and antiretroviral protease inhibitor with TRIUMEQ<br> | Drug: Riociguat (Adempas, BAY 63-2521)<br>* 0.5 mg, Oral (fasted conditions), 1 single dose<br>Drug: Antiretroviral protease inhibitor<br>* Any approved antiretroviral protease inhibitor such as atazanavir, darunavir, indinavir, ritonavir, and saquinavir ; consistent with the most recent prescribing information documents<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of riociguat |  | at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8 24 and 48 hours post-dose | 
| Cmax of riociguat |  | at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8 24 and 48 hours post-dose | 
| AUC of riociguat main metabolite M1 (BAY 60-4552) |  | at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8 24 and 48 hours post-dose | 
| Cmax of riociguat main metabolite M1 (BAY 60-4552) |  | at pre-dose and 0.5, 1, 1.5, 2, 4, 6, 8 24 and 48 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single-Dose, Open-Label, Non-Blinded, Non-Placebo-, Controlled, Stratified Design