Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Riociguat · 18 trials · 11 indications
6MWD test was used to measure the subjects functional exercise capacity. Subjects were instructed to walk alone, not run, from one end to the other end of the walking course, at their own pace, while attempting to cover as much ground as possible in 6 minutes. No "warm-up" period was performed before the test. Investigators have not walked with the subjects. This was an encouraged test (the person conducting the test encouraged subjects to walk farther or faster by using only standardized phrases).
Analyses of drug-related TEAEs were based on the assessment of causal relationship to study medication.
Analyses of deaths were based on the assessment of causal relationship to study medication. The safety follow-up visit was to be performed 30 days after the last dose of riociguat.
Analyses of deaths were based on the assessment of causal relationship to study medication. The safety follow-up visit was to be performed 30 days after the last dose of riociguat.
6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.
6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.
Digital ulcer net burden is defined as the total number of "active" and indeterminate digital ulcers at an assessment. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization.
The mRSS is a validated physical examination method for estimating skin thickness. It correlates with biopsy measures of collagen in the dermis and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3+ (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 (higher score means worse situation) and is used to categorize severity of SSc. A decrease in the mean change of mRSS shows mRSS improved.
Systolic blood pressure (SBP) was measured as standard vital sign parameter. Range allowed in this study: \<= 180 mmHg. In addition, SBP must be \>=95 mmHg in the first 2 hours after intake of background treatment with sildenafil. The maximum change from baseline at each visit was defined as the within-subject maximum decrease from baseline (or zero if baseline was lower than all subsequent SBP measurements in that profile) within 4 hours post-dose. Baseline was the last SBP recorded at and within 30 minutes before intake of study drug.
AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC is defined as area under concentration versus time curve from time 0 (predose) to extrapolated infinite time. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of plasma samples and measuring the concentrations of drug in each sample. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Area under the plasma concentration vs time curve from zero to infinity for total (bound and unbound) drug after single dose for BAY 63-2521 and its metabolite M1 (BAY 60-4552)
Maximum total (bound and unbound) drug concentration in plasma after single dose administration for BAY 63-2521 and its metabolite M1
Half-life associated with the terminal slope for BAY 63-2521 and its metabolite M1
Fraction unbound for BAY 63-2521 and its metabolite M1
AUC for unbound drug for BAY 63-2521 and its metabolite M1
Cmax for unbound drug for BAY 63-2521 and its metabolite M1
PAPmean was reported during right heart catheterization
PVR was calculated according to the formula PVR = 80\*(PAPmean - pulmonary capillary wedge pressure)/cardiac output
| Arm | Type | Description |
|---|---|---|
| Riociguat | EXPERIMENTAL | Subjects received riociguat film coated immediate-release (IR) tablet 3 times a day (tid) with or without food at a starting dose of 1.0 milligram (mg) and increased by 0.5 mg increments at 2-weekly intervals to a maximum of 2.5 mg tid, until Week 8 (titration phase). An optimal dose was determined based on systolic blood pressure (SBP) and well-being. Thereafter, riociguat continued at the optimal individual dose until Week 24 (Main phase). Dose reductions or stop of study medication for safety reasons were allowed at any time. Increases or re-increases in 0.5 mg steps (maximum dose 2.5 mg) were possible at the investigator's discretion weighing the benefit with potential risks implied. Subjects were offered participation in EDSP and received riociguat 2.5 mg film coated IR tablet 3 tid with or without food for 18 months or until reimbursement. |
| Arm 1 | EXPERIMENTAL | - |
| Riociguat (Adempas, BAY63-2521)_individual dose titration | EXPERIMENTAL | Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 16 weeks |
| Placebo | PLACEBO_COMPARATOR | Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks |
| Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT | EXPERIMENTAL | Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks |
| Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT | EXPERIMENTAL | Participants received Riociguat orally as a film-coated tablet up to 1.5mg three times daily (tid) (titration between 1.0 mg and 1.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks |
| Riociguat+Placebo | EXPERIMENTAL | Randomization order 1: first single oral dose of 2 mg BAY63-2521, then matching placebo |
| Placebo+Riociguat | EXPERIMENTAL | Randomization order 2: first matching placebo, then single oral dose of 2 mg BAY63-2521 |
| Riociguat and ATRIPLA | EXPERIMENTAL | - |
| Riociguat and COMPLERA | EXPERIMENTAL | - |
| Riociguat and STRIBILD | EXPERIMENTAL | - |
| Riociguat and TRIUMEQ | EXPERIMENTAL | - |
| Riociguat and antiretroviral protease inhibitor with TRIUMEQ | EXPERIMENTAL | - |
| BAY63-2521 with Non sparkling water | EXPERIMENTAL | Single dose of a whole 2.5 mg riociguat tablet (fasted) with 240 mL of non-sparkling water at room temperature |
| BAY63-2521 with applesauce | EXPERIMENTAL | Single dose of a crushed 2.5 mg riociguat tablet suspended in 50 mL applesauce, to be eaten with a spoon (fasted) |
| BAY63-2521 with water | EXPERIMENTAL | Single dose of a crushed 2.5 mg riociguat tablet suspended in a glass with 25 mL water, to be drunk and flushed twice with 25 mL water in the same glass (fasted) |
| BAY63-2521 after breakfast | EXPERIMENTAL | Single dose of a whole 2.5 mg riociguat tablet taken within 5 minutes after the last bite of a continental breakfast (fed) with 240 mL of non-sparkling water at room temperature |
| Arm 2 | EXPERIMENTAL | - |
| Arm 3 | EXPERIMENTAL | - |
| Arm 4 | EXPERIMENTAL | - |
| Arm 5 | EXPERIMENTAL | - |
| Riociguat, Child Pugh A | EXPERIMENTAL | Participants with liver cirrhosis and mild hepatic impairment received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, Child Pugh B | EXPERIMENTAL | Participants with liver cirrhosis and moderate hepatic impairment received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, control A | EXPERIMENTAL | Healthy age-, weight-, and gender- matched participants to Child Pugh A group received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, control B | EXPERIMENTAL | Healthy age-, weight-, and gender- matched participants to Child Pugh B group received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, healthy participants | EXPERIMENTAL | Participants with creatinine clearance (CLCR) \>80 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, mild renal impairment | EXPERIMENTAL | Participants with CLCR 50-80 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, moderate renal impairment | EXPERIMENTAL | Participants with CLCR 30-\<50 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, severe renal impairment | EXPERIMENTAL | Participants with CLCR \<30 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | EXPERIMENTAL | Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3. |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | EXPERIMENTAL | Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3. |
| Name | Type | Description |
|---|---|---|
| Riociguat (Adempas, BAY63-2521) | DRUG | Riociguat / BAY63-2521 film-coated tablets will be used in this study at a dosage of either 0.5, 1.0, 1.5, 2.0, and 2.5 mg. 3 times daily |
| Riociguat (BAY63-2521) | DRUG | BAY63-2521: 1mg tid -2.5 mg tid oral until end of study |
| Placebo | DRUG | Matching Placebo tid orally for 16 weeks |
| Riociguat | DRUG | riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered) |
| Sildenafil | DRUG | Participants continued to take daily stable sildenafil background treatment according to their prescriptions. |
| Riociguat (Adempas, BAY63-2521). | DRUG | BAY63-2521 will be up-titrated from 1,0 mg TID to 2,5 mg TID |
| Riociguat (Adempas, BAY 63-2521) | DRUG | 0.5 mg, Oral (fasted conditions), 1 single dose |
| ATRIPLA | DRUG | 600 mg efavirenz, 200 mg emtricitabine, and 300 mg tenofovir disoproxil fumarate, i.e. 1 tablet, once daily |
| COMPLERA | DRUG | 200 mg emtricitabine, 25 mg rilpivirine, and 300 mg tenofovir disoproxil fumarate, i.e. 1 tablet, once daily |
| STRIBILD | DRUG | 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 300 mg tenofovir disoproxil fumarate, i.e. 1 tablet, once daily |
| TRIUMEQ | DRUG | 600 mg abacavir, 50 mg dolutegravir, and 300 mg lamivudine, i.e. 1 tablet, once daily |
| Antiretroviral protease inhibitor | DRUG | Any approved antiretroviral protease inhibitor such as atazanavir, darunavir, indinavir, ritonavir, and saquinavir ; consistent with the most recent prescribing information documents |
| Riociguat(Adempas,BAY63-2521) | DRUG | Single dose of a whole 2.5 mg riociguat tablet |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | DRUG | 1.0 mg BAY63-2521 will be given twice per subject, as single dose administration during the hemodynamic investigation (on study day 1) and during the lung function testing (on study day 3). |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | DRUG | 2.5 mg BAY63-2521 will be given twice per subject, as single dose administration during the hemodynamic investigation (on study day 1) and during the lung function testing (on study day 3). |
Inclusion Criteria: * Male or female patients (18 -75 years of age) with idiopathic, familial, drug/toxin induced and associated PAH due to congenital heart disease (Group I / Dana Point Classification of PH) demonstrating insufficient response to treatment with PDE-5i for at least 3 months * Patie...
Riociguat is an investigational small molecule being studied for scleroderma, Raynaud disease, and HIV drug-drug interactions. It is also evaluated in clinical pharmacology studies. The drug is in Phase 1 clinical development and is not approved for any indication.
Riociguat is developed by Bayer AG, a company traded under the ticker BAYRY. Bayer is conducting Phase 1 clinical trials to evaluate the drug's safety, tolerability, and pharmacokinetics.
Riociguat is in Phase 1 clinical development. All six completed trials were Phase 1 studies, with no active trials currently ongoing. The drug remains investigational and has not received regulatory approval.
Riociguat has completed six Phase 1 trials, including NCT01489488, NCT02159313, NCT04364464, and NCT04366622. These studies evaluated bioavailability, food effects, and the impact of renal and hepatic impairment on the drug's pharmacokinetics.
Riociguat is also known as BAY 63-2521. Clinical trial records refer to the drug by this alternative name, particularly in studies assessing its safety, tolerability, and how the body absorbs, distributes, and eliminates the medication.