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Effect of Riocigaut on Cerebral Vasodilation and Headache Induction in Healthy Volunteers

Primary Purpose

Headache

Status

Recruiting

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

Dose Riociguat 2,5 or 5mg

Riociguat

Placebo

About this trial

This is an interventional other trial for Headache

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Ability to provide written informed consent and receive participant privacy and rights information.
Male or female participants aged 18-45 years.
Weight between 50-100kg
Non-smokers

Exclusion Criteria:

Any current or previous known primary or secondary headache disorder(s) apart from tension type headache ≤ 1 day per month.
Headache <48 hours before study start.
Daily use of any medication except contraceptives. Specifically use of nitrates or nitric oxide donors or phosphodiesterase inhibitors.
Intake of any pro necessitate medication later than 4 times plasma half-life for the specific drug before study start, except for contraceptives
Women of child-bearing potential not currently using safe contraceptives. Women of child-bearing potential does not include hysterectomized women and women who have been in menopause for at least 2 years. Safe contraceptives include either IUD, birth control pills, surgical sterilization of the woman, depositary gestagen, barrier prevention or sexual abstinence.
Pregnant or breastfeeding women
Positive pregnancy urin screening on screening day or study days.
A medical history or clinical signs of
- Hypertension (systolic blood pressure >140mmHg and/or diastolic blood pressure >90mmHg)
- Hypotension (systolic blood pressure <100mmHg and/or diastolic blood pressure <50mmHg)
Electrocardiogram (ECG) with any clinically significant abnormalities at screening determined by the investigator, including but not limited to, prolonged PQ or QTc interval, signs of arrythmias, ischemia or left/right ventricle dysfunction/hypertrophy.
Blood work at screening with signs of anemia.
Blood work at screening with signs of abnormal kidney and liver function.
A medical history or clinical signs of cardiovascular disease including cerebrovascular disease.
A medical history or clinical signs of pulmonary disease.
A medical history or clinical signs of liver, renal, gastrointestinal, endocrine, hematological or neurological disease.
A medical history or clinical signs of psychiatric illness or substance abuse
A medical history or clinical signs of drug or alcohol abuse
A medical history or clinical signs of disease of any origin that the investigative doctor finds relevant for participation in the study
A family history of severe cardiac disease.
Any history of hypersensitivity to riociguat.
Subjects who do not want information about crucial pathological findings during the study

Sites / Locations

Danish Headache CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Dose Riociguat 2,5 or 5mg

Riociguat

Placebo

Arm Description

Riociguat dose finding pilot experiment, 2,5mg and 5mg

Riociguat orally

Placebo orally

Outcomes

Primary Outcome Measures

Change in superficial temporal artery (STA) diameter from baseline to 90 minutes in healthy volunteers after receiving riociguat compared to placebo, measured by high resolution ultrasonography.

Secondary Outcome Measures

Change in middle cerebral artery (MCA) blood flow velocity in healthy volunteers after receiving riociguat compared to placebo, measured by transcranial doppler from baseline until 4 hours after intake.

Changes in heart rate in healthy volunteers after receiving riociguat compared to placebo.

Incidence of headache (>0 on Numeric Rating Scale (NRS) from 0 to 10, 0="no pain" versus 1-10="pain") in healthy volunteers until 12 hours after receiving riociguat compared to placebo.

Data will be collected with a questionnaire.

Full Information

NCT ID

NCT05582811

First Posted

October 10, 2022

Last Updated

February 14, 2023

Sponsor

Danish Headache Center

1. Study Identification

Unique Protocol Identification Number

NCT05582811

Brief Title

Effect of Riocigaut on Cerebral Vasodilation and Headache Induction in Healthy Volunteers

Official Title

Riociguat (BAY 63-2521), a Stimulator of Soluble Guanylate Cyclase (sGC) - Cerebral Vasodilation and Headache Induction in Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 26, 2022 (Actual)

Primary Completion Date

January 1, 2024 (Anticipated)

Study Completion Date

January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Danish Headache Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This double-blind, randomized, placebo-controlled cross-over clinical trial aims to investigate the effects of riocigaut on cerebral arteries and headache inducing properties in healthy volunteers.

Detailed Description

The investigators believe that activation of sGC could play a role in migraine pathophysiology and propose that stimulation with riociguat causes cranial arterial dilation alongside headache in healthy volunteers. Twelve healthy volunteers participate at a screening visit, and if eligible, on two separate study days, where participants, in a randomized cross-over fashion, will ingest either riociguat (active comparator arm) or placebo (placebo comparator arm), serving as their own controls. On the two separate study days the investigators will measure change in diameter of superficial temporal artery and middle cerebral artery blood flow velocity and register possible headache until 4 hours after intake of riociguat or placebo. At home participants are expected to fill out a headache diary until 12 hours from intake of riociguat or placebo. Leading up to the main study described above, the investigators will conduct a pilot dose-finding study (experimental arm) of increasing doses of riociguat, 2,5mg and 5mg respectively, on two separate study days in 5 healthy volunteers, to ensure an appropriate dose is applied in the main study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Headache

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

17 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dose Riociguat 2,5 or 5mg

Arm Type

Experimental

Arm Description

Riociguat dose finding pilot experiment, 2,5mg and 5mg

Arm Title

Riociguat

Arm Type

Active Comparator

Arm Description

Riociguat orally

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo orally

Intervention Type

Drug

Intervention Name(s)

Dose Riociguat 2,5 or 5mg

Intervention Description

A selective stimulator of soluble guanylate cyclase (sGC)

Intervention Type

Drug

Intervention Name(s)

Riociguat

Intervention Description

A selective stimulator of soluble guanylate cyclase (sGC)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Change in superficial temporal artery (STA) diameter from baseline to 90 minutes in healthy volunteers after receiving riociguat compared to placebo, measured by high resolution ultrasonography.

Time Frame

0 - 90 minutes

Secondary Outcome Measure Information:

Title

Time Frame

0 - 4 hours

Title

Changes in heart rate in healthy volunteers after receiving riociguat compared to placebo.

Time Frame

0 - 4 hours

Title

Incidence of headache (>0 on Numeric Rating Scale (NRS) from 0 to 10, 0="no pain" versus 1-10="pain") in healthy volunteers until 12 hours after receiving riociguat compared to placebo.

Description

Data will be collected with a questionnaire.

Time Frame

0 - 12 hours

Other Pre-specified Outcome Measures:

Title

Severity of headache, if headache occurs, in healthy volunteers after receiving riociguat compared to placebo, rated on 11-point NRS from 0 ("no pain") to 10 ("worst pain imaginable") from baseline to 12 hours after intake.

Description

Data will be collected with a questionnaire.

Time Frame

0 - 12 hours

Title

Headache characteristics, if headache occurs, in healthy volunteers after receiving riociguat compared to placebo, rated from baseline to 12 hours after intake.

Description

Data will be collected with a questionnaire.

Time Frame

0 - 12 hours

Title

Reported use of rescue medication if headache occurs, in healthy volunteers, after receiving riociguat compared to placebo.

Description

To evaluate need for rescue medication. Data will be collected with a questionnaire.

Time Frame

0 - 12 hours

Title

Time course of STA diameter from baseline until 4 hours after receiving riociguat compared to placebo.

Description

Measured by high resolution ultrasonography.

Time Frame

0 - 4 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability to provide written informed consent and receive participant privacy and rights information. Male or female participants aged 18-45 years. Weight between 50-100kg Non-smokers Exclusion Criteria: Any current or previous known primary or secondary headache disorder(s) apart from tension type headache ≤ 1 day per month. Headache <48 hours before study start. Daily use of any medication except contraceptives. Specifically use of nitrates or nitric oxide donors or phosphodiesterase inhibitors. Intake of any pro necessitate medication later than 4 times plasma half-life for the specific drug before study start, except for contraceptives Women of child-bearing potential not currently using safe contraceptives. Women of child-bearing potential does not include hysterectomized women and women who have been in menopause for at least 2 years. Safe contraceptives include either IUD, birth control pills, surgical sterilization of the woman, depositary gestagen, barrier prevention or sexual abstinence. Pregnant or breastfeeding women Positive pregnancy urin screening on screening day or study days. A medical history or clinical signs of Hypertension (systolic blood pressure >140mmHg and/or diastolic blood pressure >90mmHg) Hypotension (systolic blood pressure <100mmHg and/or diastolic blood pressure <50mmHg) Electrocardiogram (ECG) with any clinically significant abnormalities at screening determined by the investigator, including but not limited to, prolonged PQ or QTc interval, signs of arrythmias, ischemia or left/right ventricle dysfunction/hypertrophy. Blood work at screening with signs of anemia. Blood work at screening with signs of abnormal kidney and liver function. A medical history or clinical signs of cardiovascular disease including cerebrovascular disease. A medical history or clinical signs of pulmonary disease. A medical history or clinical signs of liver, renal, gastrointestinal, endocrine, hematological or neurological disease. A medical history or clinical signs of psychiatric illness or substance abuse A medical history or clinical signs of drug or alcohol abuse A medical history or clinical signs of disease of any origin that the investigative doctor finds relevant for participation in the study A family history of severe cardiac disease. Any history of hypersensitivity to riociguat. Subjects who do not want information about crucial pathological findings during the study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nadja Rasmussen, MD

Phone

+4538633557

nadja.bredo.rasmussen@regionh.dk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Messoud Ashina, MD

Organizational Affiliation

Danish Headache Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Danish Headache Center

City

Copenhagen

State/Province

Glostrup

ZIP/Postal Code

2600

Country

Denmark

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nadja B Rasmussen, MD

Phone

+4538633557

nadja.bredo.rasmussen@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD

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Effect of Riocigaut on Cerebral Vasodilation and Headache Induction in Healthy Volunteers

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