Relative Bioavailability and Food Effect Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01489488
First received: December 8, 2011
Last updated: June 29, 2015
Last verified: June 2015
  Purpose

Primary objective: To determine oral bioavailability of the liquid formulation intended for pediatric use and potential food effects in healthy adults.

Secondary objective: To evaluate safety and tolerability measured by physical examination findings, vital signs, electrocardiogram (ECG), laboratory parameters, and adverse events (AEs).


Condition Intervention Phase
Pharmacology, Clinical
Drug: Riociguat (BAY63-2521)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Relative Bioavailability and Food Effect Study of Two Oral Liquid Formulations in Comparison to a 1 mg Tablet of Riociguat to Characterize Its Pharmacokinetic Properties in Healthy Male and Female Adult Subjects in a Randomized, Open Label, 5-fold Crossover Design

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and its Analyte M1 (BAY60-4552) [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Maximum Observed Drug Concentration (Cmax) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Area Under the Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

  • Maximum Observed Drug Concentration Adjusted by Dose (Cmax/D) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    Geometric mean and percentage geometric coefficient of variation (%CV) were reported.


Secondary Outcome Measures:
  • Area Under the Concentration Versus Time Curve From Zero to Infinity Divided by Dose per Kilogram Body Weight (AUC,norm) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. AUCnorm is defined as AUC divided by dose per kg body weight.

  • Maximum Observed Plasma Concentration Divided by Dose per Kilogram Body Weight (Cmax,norm) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. Cmax,norm is defined as Cmax divided by dose per kg body weight.

  • Time to Reach Maximum Drug Concentration in Plasma (tmax) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.

  • Terminal Half Life (t1/2) of Riociguat and its Analyte M1 (BAY60-4552) [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    Half life associated with terminal slope refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in hours and derived from the terminal slope of the concentration versus time curve. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

  • Mean Residence Time (MRT) of Riociguat and its Analyte M1 (BAY604552) [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    MRT is an average duration of the drug in the body, and is expressed in hours.

  • Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration (AUC[0-tlast]) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    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(0-tlast) is defined as AUC from time zero to the last data point above the lower limit of quantification. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

  • Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Divided by Dose per Kilogram Body Weight (AUC[0-tlast]norm) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    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(0-tlast), norm is defined as AUC from time zero to the last data point above the lower limit of quantification divided by dose per kg body weight. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.

  • Area Under the Concentration Versus Time Curve From Zero to Last Quantifiable Concentration Divided by Dose (AUC[0-tlast]/D) of Riociguat and its Analyte M1 (BAY60-4552) After a Single Dose [ Time Frame: 0 hour (predose), 15, 30, 45 minutes; 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48, and 72 hours postdose ] [ Designated as safety issue: No ]
    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(0-tlast)/D is defined as AUC from time zero to the last data point above the lower limit of quantification divided by dose. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.


Enrollment: 32
Study Start Date: January 2012
Study Completion Date: May 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Riociguat (BAY63-2521)
Single oral dose of 2.4 milligram (mg) riociguat (BAY63-2521) as pediatric high-concentration suspension (0.15 mg per milliliter [mg/mL], i.e. 16 mL) under fasting conditions
Experimental: Arm 2 Drug: Riociguat (BAY63-2521)
Single oral dose of 2.4 mg riociguat as pediatric high-concentration suspension (0.15 mg/mL, i.e. 16 mL) under fed conditions
Experimental: Arm 3 Drug: Riociguat (BAY63-2521)
Single oral dose of 0.3 mg riociguat as pediatric high-concentration suspension (0.15 mg/mL, i.e. 2 mL) under fasting conditions
Experimental: Arm 4 Drug: Riociguat (BAY63-2521)
Single oral dose of 0.15 mg riociguat as pediatric low-concentration suspension (0.03 mg/mL, i.e. 5 mL) under fasting conditions
Experimental: Arm 5 Drug: Riociguat (BAY63-2521)
Single oral dose of riociguat immediate release (IR) tablet 1 mg under fasting conditions

Detailed Description:

Clinical pharmacology

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male or female volunteers
  • Age 18-45 years
  • Body mass index (BMI) 18.0-29.9 kg/m²
  • Systolic blood pressure (SBP) 110-145 mmHg
  • No drugs 2 weeks before treatment
  • Nonsmokers for at least 12 weeks

Exclusion Criteria:

  • Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
  • Medical disorder that would impair the subject's ability to complete the study in the opinion of the Investigator
  • Known hypersensitivity to the study drugs (active substance or excipients of the preparations)
  • Known severe allergies, non-allergic drug reactions, or multiple drug allergies
  • Relevant diseases within the last 4 weeks prior to the first study drug administration
  • Regular use of medicines
  • Regular use of therapeutic or recreational drugs
  • Use of any medication within the 2 weeks preceding the study
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01489488

Locations
Germany
Köln, Nordrhein-Westfalen, Germany, 51063
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01489488     History of Changes
Other Study ID Numbers: 14986, 2011-001893-24
Study First Received: December 8, 2011
Last Updated: June 29, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Relative bioavailability study

ClinicalTrials.gov processed this record on August 27, 2015