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

Headache Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05582811
• Other study ID #: H-22020347
• Status: Completed
• Phase: N/A
• Start date: October 26, 2022
• Est. completion date: June 1, 2023

Study information

• Verified date: January 2024
• Source: Danish Headache Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: June 1, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache

Intervention

Drug:
• Dose Riociguat 2,5 or 5mg
A selective stimulator of soluble guanylate cyclase (sGC)
• Riociguat
A selective stimulator of soluble guanylate cyclase (sGC)
• Placebo
Placebo

Locations

Country	Name	City	State
Denmark	Danish Headache Center	Copenhagen	Glostrup

Sponsors (1)

Lead Sponsor	Collaborator
Danish Headache Center

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Data will be collected with a questionnaire.	0 - 12 hours
Other	Headache characteristics, if headache occurs, in healthy volunteers after receiving riociguat compared to placebo, rated from baseline to 12 hours after intake.	Data will be collected with a questionnaire.	0 - 12 hours
Other	Reported use of rescue medication if headache occurs, in healthy volunteers, after receiving riociguat compared to placebo.	To evaluate need for rescue medication. Data will be collected with a questionnaire.	0 - 12 hours
Other	Time course of STA diameter from baseline until 4 hours after receiving riociguat compared to placebo.	Measured by high resolution ultrasonography.	0 - 4 hours
Primary	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.	0 - 90 minutes
Secondary	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.	0 - 4 hours
Secondary	Changes in heart rate in healthy volunteers after receiving riociguat compared to placebo.	Measured by heart rate	0 - 4 hours
Secondary	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.	0 - 12 hours