Pilot Study of the Effect of a Substance P Antagonist, Aprepitant, on the Secretion of Aldosterone in Patients with Obstructive Sleep Apnea and Arterial Hypertension Syndrome - (APHOS3)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

1 Jul 2024 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514837-39-00

EudraCT number

2022-001900-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The main objective of this work is to evaluate the effect of the
administration of an NK1 receptor antagonist (aprepitant) on
aldosterone secretion in patients with obstructive sleep apnea syndrome
(OSAS) and of arterial hypertension.

Secondary objectives 1

1. The secondary objectives of this work will be to evaluate the effects of the administration of an antagonist of the NK1 receptor (aprepitant) on blood pressure, renin secretion, plasma and urinary electrolytes, cortisol and ACTH, as well as the tolerance of treatment in patients with obstructive sleep apnea syndrome and arterial hypertension.

Conditions and MedDRA coding

Patients with obstructive sleep apnea syndrome with arterial hypertension

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Subject with severe obstructive sleep apnea syndrome defined by an apnea and hypopnea index (AHI) ≥ 30/h in polysomnography or ventilatory polygraphy (requiring continuous positive pressure equipment)
2. Subject with essential hypertension treated medically or by lifestyle and dietary measures or newly diagnosed (defined by SBP ≥ 140 and/or PAD ≥ 90 mmHg according to current SFHTA-HAS recommendations)
3. Patient's agreement to replace diuretics with another neutral antihypertensive treatment (which does not interfere with the reninangiotensin system) before taking the experimental treatment and throughout the study (if applicable)
4. Regulatory Criteria: o Adult aged 18 to 75 / o Affiliation to a social security scheme / o Person who has read and understood the information letter and signed the consent form / o For women: - of childbearing age, need for effective mechanical contraception (condoms) during the study and within 2 months of the last month taken, with a negative urine pregnancy test on inclusion and for the duration of the study study at V2 and V4, - postmenopausal: amenorrhea not medically induced for at least 12 months before the V1 visit

Exclusion criteria 4

1. Minor subject or subject over 75 years old
2. Criteria relating to associated pathologies leading to particular risks: o Subject with excessive daytime sleepiness with a contraindication to driving (Epworth score > 16) / o Severe uncontrolled cardiovascular disease: myocardial infarction or stroke in the last 6 months, unstable angina, heart failure. / o Knowledge of chronic renal failure defined by a glomerular filtration rate < 60 mL/min/1.73m2 for more than 3 months) or moderate hepatic failure defined by ALT and/or AST transaminases > 3N) / o Epilepsy o Known acute infections related to HIV, HBV or HCV / o Active cancer undergoing treatment or immunosuppressive treatments
3. Criteria for aprepitant: o Hypersensitivity to the active substance (aprepitant) or/and one of the excipients (contents and capsule shell) o People with hereditary problems of fructose intolerance, glucosegalactose malabsorption syndrome, or sucrase/isomaltase deficiency o Subject treated with drugs metabolized by cytochromes CYP3A4 and CYP2C9: corticosteroids (dexamethason, methylprednisolone), anti vitamin K (warfarin, acenocoumarol), benzodiazepines (midazolam, alprazolam, triazolam), anti-depressants (nefazodone), quinidine, hormonal contraceptives , ergot alkaloids (ergotamine, diergotamine), immunosuppressants (ciclosporin, tacrolimus, sirolimus, everolimus), morphine (alfentanil, fentanyl), antibiotics (rifampicin and clarithromycin-type macrolides, telithromycin), azole antifungals (ketoconazole, itraconazole, voriconazole, posaconazole), anti-virals (protease inhibitors), anti-epileptics (phenytoin, carbamazepine, phenobarbital), chemotherapies (etoposide, vinorelbine, ifosfamide, irinotecan), diuretics (tolbutamide) and herbal preparations containing St. John's wort. As well as these molecules in co-administration pimozide, terfenadine, astemizole and cisapride.
4. Placebo contraindication criteria: Lactose intolerance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 24-hour aldosteronuria measurements. At the beginning and end of each treatment period.

Secondary endpoints 1

1. blood pressure measurements, aldosteronemia, reninemia, plasma and urinary electrolytes, 24-hour plasma and urinary cortisol, plasma ACTH. At the beginning and end of each treatment period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

David MALLET

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications