CANDESARTAN for Episodic cluster headache

Inclusion criteria

• {"criterion_text":"- Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent"}
• {"criterion_text":"- Participants who have episodic cluster headacheaccording to ICHD-3 criteria present at inclusion"}
• {"criterion_text":"- Participants who have history of at least one previous bout of CH lasting > 5 weeks"}
• {"criterion_text":"- Participants that if they have other ongoing concomitant infrequent primary headache types, such as episodic migraine or episodic tension-type headache, can clearly differentiate them from attacks of CH based on the quality of pain and associated symptoms"}
• {"criterion_text":"- Participants must experience between 4 attacks per week and a maximum of 8 attacks per day of severe or very severe intensity on average over the one-week baseline period"}
• {"criterion_text":"- The cluster headache bout at the time of inclusion and baseline should exhibit characteristics consistent with the participant's typical bout"}
• {"criterion_text":"- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies: No contraceptive/barrier requirements needed for male participants; For women of childbearing potential (WOCBP), it is required that there be no ongoing pregnancy or planned pregnancies during the study period. The use of a contraception method as listed in section 10.4.2 in the protocol is mandatory."}
• {"criterion_text":"- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol"}

Exclusion criteria

• {"criterion_text":"- Chronic cluster headache excludes the participant from the study"}
• {"criterion_text":"- Primary hyperaldosteronism (Conn’s syndrome))"}
• {"criterion_text":"- Any history of severe renal insufficiency"}
• {"criterion_text":"- Hypersensitivity to candesartan, placebo or any of the excipients"}
• {"criterion_text":"- Severe hepatic impairment and/or cholestasis"}
• {"criterion_text":"- Current or recent (within last 12 months) treatment with candesartan for any indication"}
• {"criterion_text":"- Current use of other antihypertensive medication(s) including verapamil and metoprolol (see section 6.9)"}
• {"criterion_text":"- Recent initiation or change in dose (<4 months) of preventive CH medication with galcanezumab or other parenteral CGRP-inhibitors, or botulinum toxin (<6 months, fewer than 3 treatment sessions). Stable dosage with CGRP-inhibitors > 4 months and/or botulinum toxin > 6 months (at least 3 treatment sessions) is allowed"}
• {"criterion_text":"- Treatment with greater occipital nerve blocks containing steroids or oral/parental prednisone/prednisolone < 4 weeks"}
• {"criterion_text":"- Recent initiation (< 4 weeks) of oral preventive CH medications including indomethacin or oral gepants (preventive use)"}
• {"criterion_text":"- Current use of potassium supplements"}
• {"criterion_text":"- CH due to known structural lesion"}
• {"criterion_text":"- Current use of spironolactone"}
• {"criterion_text":"- Current use of Lithium"}
• {"criterion_text":"- Current or recent (< 4 weeks) participation in other relevant clinical studies"}
• {"criterion_text":"- Current bout of ECH lasting >4 weeks before possible initiation of IMP. The onset of the bout is defined as the period when the headache frequency (of severe or very severe intensity) ranges from one every other day to eight per day for at least 7 consecutive days"}
• {"criterion_text":"- Abuse of alcohol or illicit drugs"}
• {"criterion_text":"- Women of child-bearing age without contraception"}
• {"criterion_text":"- Inability to understand study procedures and to comply with them for the entire length of the study"}
• {"criterion_text":"- Any previous surgical treatment for CH like deep brain stimulation, microvascular decompression, gamma knife radiosurgery, neurostimulation or other invasive treatments"}
• {"criterion_text":"- Current chronic migraine or chronic tension-type headache (migraine or tension-type headache that has met the ICHD-3 criteria for these conditions within the past 12 months)"}
• {"criterion_text":"- Requiring detoxification from opioids (medication overuse headache (MOH) in itself is not an exclusion criterium)"}
• {"criterion_text":"- Pregnancy, planning to get pregnant, inability to use contraceptives (See inclusion criteria, number 7), and lactating"}
• {"criterion_text":"- Severe depression or other psychiatric disorder that may interfere with the treatment"}
• {"criterion_text":"- Other severe chronic pain conditions that may interfere with the study, including trigeminal neuralgia"}
• {"criterion_text":"- History of angioneurotic edema due to candesartan or other antihypertensive medication(s)"}

Primary endpoints

• {"endpoint_text":"- Change in the weekly frequency of severe and very severe cluster headache attacks from the pre-randomization diary during the three-week blinded phase","definition_or_measurement_approach":"Change measured versus the pre-randomization (one-week) diary over the three-week blinded treatment phase (weekly frequency of severe and very severe attacks)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in total attack frequency of cluster headache attacks during the three-week blinded phase","definition_or_measurement_approach":"Change from baseline (pre-randomization diary) in total attack frequency during the three-week blinded phase."}
• {"endpoint_text":"- 50% responder rate (proportion of participants with ≥50% reduction of severe and very severe attacks/week from baseline) over the blinded phase","definition_or_measurement_approach":"Proportion of participants achieving ≥50% reduction in severe/very severe attacks per week compared with baseline over the blinded phase."}
• {"endpoint_text":"- 30% responder rate (proportion of participants with ≥30% reduction of severe and very severe attacks/week from baseline) over the blinded phase","definition_or_measurement_approach":"Proportion of participants achieving ≥30% reduction in severe/very severe attacks per week compared with baseline over the blinded phase."}
• {"endpoint_text":"- 50% responder rate for each week in the blinded phase","definition_or_measurement_approach":"Weekly proportion of participants with ≥50% reduction compared with baseline, assessed for each week of the blinded phase."}
• {"endpoint_text":"- Time to sustained freedom of attacks for ≥2 months after the current bout","definition_or_measurement_approach":"Time-to-event: time until participant achieves and sustains freedom of attacks for at least 2 months after the current bout."}
• {"endpoint_text":"- Change from baseline in mean intensity of severe and very severe attacks over the blinded period","definition_or_measurement_approach":"Change from baseline in average attack intensity during the blinded period (measurement method as per protocol)."}
• {"endpoint_text":"- Change from baseline in weekly number of acute pharmacological therapies over the blinded period","definition_or_measurement_approach":"Change from baseline in weekly count of acute pharmacological treatments used during the blinded period."}
• {"endpoint_text":"- Change from baseline in weekly number of inhaled oxygen treatments over the blinded period","definition_or_measurement_approach":"Change from baseline in weekly number of inhaled oxygen treatments used during the blinded period."}
• {"endpoint_text":"- Percentage of patients who rated their improvement as 'very much better' (score of 1) or 'much better' (score of 2) on the Patient Global Impression of Improvement (PGI-I) scale at week 3, 9 and 14 after baseline.","definition_or_measurement_approach":"Proportion of participants reporting PGI-I scores of 1 or 2 at weeks 3, 9 and 14 after baseline."}
• {"endpoint_text":"- Percentage of patients who showed an improvement of more than 1 point on the HADS Anxiety (HADS-A) and/or Depression (HADS-D) subscales at weeks 3, 9, and 14 after baseline","definition_or_measurement_approach":"Proportion with >1 point improvement on HADS-A and/or HADS-D at weeks 3, 9, and 14 versus baseline."}
• {"endpoint_text":"- Assessment and evaluation of participants for suicide-related events (behavior and/or ideation) as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)","definition_or_measurement_approach":"Assessment of suicide-related events using C-SSRS per protocol schedule."}
• {"endpoint_text":"- Percentage of patients who reported a reduction of CH-specific disability at weeks 3, 9, and 14 after baseline as measured by the Cluster Headache Impact Questionnaire (CHIQ)","definition_or_measurement_approach":"Proportion reporting reduction in CH-specific disability measured by CHIQ at specified timepoints."}
• {"endpoint_text":"- Change in the weekly frequency of severe/very severe cluster headache attacks during the OTP compared with the weekly frequency in the blinded phase","definition_or_measurement_approach":"Change in weekly frequency during the open treatment period (OTP) compared with the blinded phase frequency."}
• {"endpoint_text":"- Time to recurrence of severe/very severe attacks in participants during OTP who were attack-free at the end of the blinded phase","definition_or_measurement_approach":"Time-to-event: time to recurrence of severe/very severe attacks during OTP among those attack-free at end of blinded phase."}
• {"endpoint_text":"- Proportion of participants achieving ≥50% reduction in use of weekly acute treatments in OTP compared with baseline","definition_or_measurement_approach":"Proportion with ≥50% reduction in weekly acute treatment use during OTP vs baseline."}
• {"endpoint_text":"- Time to recurrence of severe/very severe attacks in the wash-out phase in participants taking candesartan in the OTP","definition_or_measurement_approach":"Time-to-event: time to recurrence during wash-out among participants who received candesartan in OTP."}
• {"endpoint_text":"- Proportion of participants who rate their overall condition as “much improved” or “very much improved” on PGIC at Week 8 of OTP, referenced to their status at the end of the BTP","definition_or_measurement_approach":"Proportion rating condition as much/very much improved on PGIC at OTP Week 8 compared with end of blinded treatment period (BTP)."}

Methods

• Site-based recruitment through participating neurology departments and headache centers at listed hospitals in Norway and Denmark (e.g., Rigshospitalet, Helse Bergen HF, St. Olavs Hospital HF, Oslo University Hospital HF, etc.)
• Use of country-specific recruitment materials including brochures/trifold materials and recruitment film (documents: 'Recruitment material CandClus brochure episodic DK', 'K2_Recruitment material film manus CandClus2', 'K2_ Recruitment material CandClus brochure episodic NO', etc.)
• Use of a headache diary recruitment function (document: 'K2_ Recruitment material Headache diary recruitment function')
• Study public contact points listed for inquiries (e.g., candclus2@helse-bergen.no for Norway; hodepine@ntnu.no for St. Olavs Studyinfo)

Denmark

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

04-11-2025

Processing Time Days

18

Number Of Sites

1

Number Of Participants

20

Norway

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

05-11-2025

Processing Time Days

14

Number Of Sites

8

Number Of Participants

63

Primary sponsor

Full Name

Helse Bergen HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway

Third parties

• {"country":"Norway","full_name":"Kragero Tablettproduksjon AS","duties_or_roles":"sponsorDuties code 14","organisation_type":"Pharmaceutical company"}

Co-sponsors

• St. Olavs Hospital HF