Clinical Trial Results:
Single dose, double-blind, placebo-controlled, single center, randomized cross-over study to investigate safety, tolerability, pharmacodynamics and pharmacokinetic properties of BAY-632521 after oral dosing of a 2 mg IR tablet in 20 subjects with Raynaud’s phenomenon (RP)
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Summary
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EudraCT number |
2013-001899-38 |
Trial protocol |
DE |
Global end of trial date |
07 Nov 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Sep 2016
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First version publication date |
12 Jun 2016
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAY63-2521/16787
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01926847 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bayer AG
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Sponsor organisation address |
Kaiser-Wilhelm-Allee, D-51368, Leverkusen, Germany,
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Public contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Scientific contact |
Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Nov 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Nov 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study was to investigate the safety, tolerability and pharmacodynamics of a single oral dose of riociguat (BAY63-2521) administered in subjects suffering from Raynaud’s phenomenon.
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects and/or their legally authorized representative. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Oct 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 23
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Worldwide total number of subjects |
23
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EEA total number of subjects |
23
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
21
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Study was conducted at one study center in Germany, between 07 October 2013 (first subject first visit) and 04 June 2014 (last subject last visit). | |||||||||||||||
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Pre-assignment
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Screening details |
All 23 subjects who were randomized, received either placebo or riociguat treatment once, in a cross-over fashion, during the respective intervention periods. | |||||||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo – Riociguat (Adempas; BAY63-2521) | |||||||||||||||
Arm description |
Subjects who followed treatment sequence placebo then riociguat (Adempas; BAY63-2521) were reported. Single oral dose of matching placebo in the first intervention period; followed by single oral dose of riociguat (Adempas; BAY63-2521) 2 milligram (mg) tablet in the second intervention period. A wash-out phase of 1 week was maintained between treatments. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Each subject received a single oral dose of placebo matched to riociguat (BAY63-2521) during the first intervention period of the study.
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Investigational medicinal product name |
Riociguat
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Investigational medicinal product code |
BAY63-2521
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Other name |
Adempas
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Each subject received a single oral dose of 2 mg riociguat during the first intervention period of the study.
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Arm title
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Riociguat (Adempas; BAY63-2521)–Placebo | |||||||||||||||
Arm description |
Subjects who followed treatment sequence riociguat (Adempas; BAY63-2521) then placebo were reported. Single oral dose of riociguat (Adempas; BAY63-2521) 2 mg tablet in the first intervention period; followed by single oral dose of matching placebo in the second intervention period. A wash-out phase of 1 week was maintained between treatments. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Riociguat
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Investigational medicinal product code |
BAY63-2521
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Other name |
Adempas
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Each subject received a single oral dose of 2 mg riociguat during the first intervention period of the study.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Each subject received a single oral dose of placebo matched to riociguat (BAY63-2521) during the second intervention period of the study.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo – Riociguat (Adempas; BAY63-2521)
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Reporting group description |
Subjects who followed treatment sequence placebo then riociguat (Adempas; BAY63-2521) were reported. Single oral dose of matching placebo in the first intervention period; followed by single oral dose of riociguat (Adempas; BAY63-2521) 2 milligram (mg) tablet in the second intervention period. A wash-out phase of 1 week was maintained between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Riociguat (Adempas; BAY63-2521)–Placebo
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Reporting group description |
Subjects who followed treatment sequence riociguat (Adempas; BAY63-2521) then placebo were reported. Single oral dose of riociguat (Adempas; BAY63-2521) 2 mg tablet in the first intervention period; followed by single oral dose of matching placebo in the second intervention period. A wash-out phase of 1 week was maintained between treatments. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo – Riociguat (Adempas; BAY63-2521)
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Reporting group description |
Subjects who followed treatment sequence placebo then riociguat (Adempas; BAY63-2521) were reported. Single oral dose of matching placebo in the first intervention period; followed by single oral dose of riociguat (Adempas; BAY63-2521) 2 milligram (mg) tablet in the second intervention period. A wash-out phase of 1 week was maintained between treatments. | ||
Reporting group title |
Riociguat (Adempas; BAY63-2521)–Placebo
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Reporting group description |
Subjects who followed treatment sequence riociguat (Adempas; BAY63-2521) then placebo were reported. Single oral dose of riociguat (Adempas; BAY63-2521) 2 mg tablet in the first intervention period; followed by single oral dose of matching placebo in the second intervention period. A wash-out phase of 1 week was maintained between treatments. | ||
Subject analysis set title |
Safety analysis set (SAF)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects who received one dose of the study medication were included in the safety evaluation.
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Subject analysis set title |
Pharmacodynamic analysis set (PDS)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All subjects who completed the study without major protocol deviations were included in the evaluation of pharmacodynamics.
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Subject analysis set title |
Pharmacokinetic (PK) analysis set (PKS)
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All subjects who received one dose of the study medication and had a valid pharmacokinetic profile were included in the analysis of pharmacokinetic data.
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Subject analysis set title |
Placebo
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects received a single oral dose of matching placebo in any intervention period.
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Subject analysis set title |
Riociguat 2 mg
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects received a single oral dose of 2 mg riociguat tablet in any intervention period.
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End point title |
Number of Subjects with Treatment Emergent Adverse Events (TEAE) [1] | |||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly and another medically important serious event as judged by the investigator. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.
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End point type |
Primary
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End point timeframe |
From start of study drug administration until Day 7 (follow-up)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [2] - SAF [3] - SAF |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Systolic Blood Pressure (SBP) at Specified Time-points [4] | |||||||||||||||||||||||||||
End point description |
SBP was measured after 10 minutes of sitting.
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End point type |
Primary
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End point timeframe |
30 minutes pre-dose; 1, 2, 3 and 4 hours post-dose
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [5] - SAF [6] - SAF |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Diastolic Blood Pressure (DBP) at Specified Time-points [7] | |||||||||||||||||||||||||||
End point description |
DBP was measured after 10 minutes of sitting.
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End point type |
Primary
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End point timeframe |
30 minutes pre-dose; 1, 2, 3 and 4 hours post-dose
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [8] - SAF [9] - SAF |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Heart Rate (HR) at Specified Time-points [10] | |||||||||||||||||||||||||||
End point description |
HR was measured after 10 minutes of sitting.
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End point type |
Primary
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End point timeframe |
30 minutes pre-dose; 1, 2, 3 and 4 hours post-dose
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [11] - SAF [12] - SAF |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Number of Subjects With Clinically Significant Laboratory Values and Haematology Assessment [13] | |||||||||
End point description |
Laboratory parameters includes aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], creatine kinase [CK], creatinine, urea, sodium, potassium and hematology includes hematocrit, hemoglobin, erythrocytes, leukocytes, platelets parameters. Number of subjects with clinically significant laboratory findings were reported.
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End point type |
Primary
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End point timeframe |
Baseline up to Day 7 (follow-up)
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [14] - SAF [15] - SAF |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Plasma Concentration at 2 - hours After Riociguat Administration [16] | ||||||||||||||||||
End point description |
A single plasma measurement for PK was done after study drug administration to evaluate the exposure at the time of the digital flow measurement. Plasma Concentration was reported based on medical grouping; diffuse cutaneous SSc, idiopathic primary SSc, limited cutaneous SSc, SSc overlap syndrome, undifferentiated form SSc. Data was planned to be reported only greater than equal to (>=) 2/3 of individual values were greater than (>) lower limit of quantification (LLOQ). Geometric mean and percentage geometric coefficient of variation (%CV) were reported. In the below table, "n" signifies subjects who were evaluable for the specified category, respectively. '99999' signified that data was not calculable as 2/3 of individual had value < LLOQ.
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End point type |
Primary
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End point timeframe |
At 2 hours post-dose
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| Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [17] - PKS |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Placebo Corrected Change in Digital Blood Flow at Room Temperature, Measured by Laser Doppler Perfusion Imaging [18] | ||||||||||||||||||
End point description |
The digital blood flow in the index finger of the right hand was measured 2 times before and 2 hours after intake of riciguat or placebo respectively using laser doppler perfusion imaging and measured by Laser Speckle Contrast Analysis (LASCA). Mean value was calculated for the 2 measures.
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End point type |
Primary
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End point timeframe |
Baseline (0 minutes), 2 hours post-dose
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| Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [19] - PDS [20] - PDS |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Placebo Corrected Change in Digital Blood Flow During Cold Exposure, Measured by Laser Doppler Perfusion Imaging [21] | ||||||||||||||||||
End point description |
The digital blood flow in the index finger of the right hand was measured 2 times before and 2 hours after intake of riciguat or placebo respectively using laser doppler perfusion imaging and measured by Laser Speckle Contrast Analysis (LASCA). Mean value was calculated for the 2 measures.
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End point type |
Primary
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End point timeframe |
Baseline (0 minutes), 2 hours post-dose
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| Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were done, no inferential statistical analyses were performed. |
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| Notes [22] - PDS [23] - PDS |
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Treatment-emergent adverse events were collected from the start of study treatment until the end of follow-up (7 days post-dose)
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received a single oral dose of matching placebo in any intervention period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Riociguat 2 mg
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Reporting group description |
Subjects received a single oral dose of 2 mg riociguat tablet in any intervention period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Occurrence of "±” in relation with geometric CV is autogenerated and cannot be deleted. ‘99999’ in the posting indicates that data were not calculated. Decimal places were automatically truncated if last decimal equals zero. | |||
