Synergy Osa

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 Dec 2024 → ongoing

Decision date (initial)

2024-09-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Desitin Arzneimittel GmbH, Hamburg, Germany

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Diagnosis, Therapy, Efficacy

Efficacy, safety, and tolerability of the carbonic anhydrase inhibitor sulthiam (STM) in a randomized, cross over, double-blind, placebo-controlled study comparing STM and placebo in addition to an OAT in patients with an incomplete therapeutic response to the OAT alone.

Secondary objectives 1

1. Identification of biomarkers and efficacy of two types of intervention in OSA patients with an insufficient therapeutic effect of an OAT after STM vs. placebo in a 2 week cross over protocol. Evaluation of conventional metrics of OSA using two principally different therapies (alone and in combination with respect to endotypic traits and hypoxia related measures in this disease.

Conditions and MedDRA coding

Obstructive sleep apnea with an incomplete clinical response to oral appliance therapy.

Regulatory references

Plan to share IPD

No

IPD plan description

No data sharing with Desitin GmBH.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. AHI3a ≥15
2. Provision of informed consent after the scope and nature of the study have been explained prior to any study specific procedures.
3. Able to speak, read and understand the local language and possess the ability to respond to questions, follow instructions, complete questionnaires, and comply with the study procedures.
4. Male or female gender and aged 18 to 75 years (both inclusive).

Exclusion criteria 23

1. Patients fulfilling criteria for a dominant central sleep apnea syndrome or dominant episodes with Cheyne Stokes respiration or other clinically significant sleep disorder including periodic limb movement disorder, restless leg syndrome, periodic limb movements arousal index (PLMAI)>15, parasomnia, or narcolepsy.
2. Episode of major depression, bipolar disorder, or any other significant psychiatric disorder within the last 12 months prior to screening
3. Significant neurological or cognitive disorders including diagnosed dementia, Alzheimer’s disease, Parkinson´s disease, stroke, current epilepsy which, in the opinion of the investigator, might interfere with participation in the study
4. Renal or hepatic failure defined as limiting according to the judgement of the investigator
5. Type 1 diabetes or insulin treated type 2 diabetes or poorly controlled type 2 diabetes (HbA1c >53 mmol/mL or >7%)
6. History of actual suicidal behaviour or suicidal ideation of type 2 to 5 within one year prior to screening, or current suicidal ideation of any type (i.e., 1 to 5) as assessed by the Colombia Suicide Symptom-Rating Scale (C-SSRS) at screening
7. Patients actively participating in any active weight loss treatment program including any weight loss medication (prescription or over the counter)
8. Patients previously treated by uvulopalatopharyngoplastic surgery (UPPP) or any other type of surgery for OSA
9. Any OSA treatment within the last 3 weeks prior to baseline
10. Acute porphyria or untreated hyperthyreosis
11. An occupation designated as high risk or safety sensitive including handling complex machinery or professional drivers where there may be an increased risk for work or traffic accidents
12. Patients currently involved in shiftwork
13. Planned surgery during the study period or major surgery within 6 months before first dose
14. History of alcohol or drug abuse during the last year
15. Any clinical condition that would result in deviation from clinical routine for fitting of an OAT, according to the investigators opinion
16. Hypoventilation or hypoxemia due to COPD or other respiratory condition at the discretion of the investigator (pCO2 >6.5kPa)
17. Drug-resistant hypertension (>140/90 mmHg in spite of at least ongoing treatment with at least three drugs)
18. Patients with insufficiently treated hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg). If treated, patients must have been on the same dose of antihypertensive medication for at least 4 weeks prior to inclusion
19. Change of antihypertensive medication within the last 4 weeks prior to the randomization visit (A patient may be re-screened after 4 weeks at the discretion of the investigator providing criteria for blood pressure treatment are fulfilled)
20. Myocardial infarction or coronary vessel intervention within the previous 6 months period or unstable angina pectoris
21. Previously diagnosed or treated clinically significant cardiac arrhythmia
22. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and if at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) (See Appendix C: Guidance for Contraception and Pregnancy testing) OR A WOCBP who agrees to follow the contraceptive guidance provided during the treatment period and for at least 4 weeks after the last dose of study drug.
23. A male patient who has not been vasectomized at least 6 months before screening and partners with a WOCBP must be willing to follow the contraceptive guidance provided (See Appendix C) during the treatment period and for at least 4 weeks after the last study drug administration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reduction of the apnea/hypopnea index (AHI3a), in patients with an insufficient (AHI3a ≥15) therapeutic effect of an OAT, after STM 200 mg vs. placebo in a 2 week cross-over protocol

Secondary endpoints 7

1. Change in other OSA-related variables (AHI4), mean overnight SpO2, minimum SpO2, oxygen desaturation index 4% and hypoxic burden) as well as objective measures of sleep (sleep stages, total sleep time, arousal index, sleep efficacy) assessed by polysomnography (PSG) in patients with an insufficient therapeutic effect of an OAT after adding STM vs. placebo for 2 weeks in a cross-over protocol.
2. Exploratory endpoints including change from baseline and cross-over comparison. Effect of STM relative to placebo with respect to:
3. • Questionnaires on daytime functioning (ESS, FOSQ, CGI-S, CGI-I, PGI-S, SF-36, PGI-I, and C-SSRS) such as sleepiness, wellbeing, mood, and measures of quality of life under the dosing circumstances outlined above.
4. • Other PSG variables (NREM AHI, REM AHI, supine AHI, RERA, EEG)
5. • Effect on potential biomarkers of OSA including change in whole blood carbonic anhydrase (CA) activity, venous blood gases, concentration of carbonic anhydrase isoenzyme IX (CA-IX), circulating markers of hypoxemia including HIF-1a or phenotypic characteristics of upper airway function and stability during sleep under the dosing circumstances.
6. • Influence of conventional comorbidities in OSA, such as BMI.
7. • Change in vital signs and biochemical markers including blood pressure, glycemic control and lipids.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Center of sleep and wake disorders, Sahlgrenska Academy, University of Gothenburg

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Service desk, Sahlgrenska University Hospital

Third parties 1

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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