Study of AD981 Versus Placebo in Obesity Hypoventilation Syndrome (ATOHS)
Primary Purpose
Obesity Hypoventilation Syndrome (OHS)
Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
AD981
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obesity Hypoventilation Syndrome (OHS)
Eligibility Criteria
Inclusion Criteria:
- Be able to understand the nature of the study and sign the informed consent
- BMI > 35 kg/m2 and presence of nocturnal hypoventilation
- Previous surgical treatment for OSA is allowed if ≥ 1 year prior to enrollment
- If in treatment, CPAP or BPAP or mandibular advancement device or positional therapy intolerance or poor compliance
Exclusion Criteria:
- Narcolepsy, craniofacial malformation, renal failure, hepatic disease, schizophrenia, schizoaffective disorder or bipolar disorder, cognitive dysfunction, severe neurological disorder, pheochromocytoma, adrenocortical insufficiency, hyperchloremic acidosis.
- Respiratory (COPD, ILD, oxygen therapy) or cardiac (Heart Failure, Atrial fibrillation, established severe peripheral arterial disease) disease or hypertension requiring more than 3 medications for control
- Cardiomyopathies, heart malformation or structural heart alterations, severe rhythm disorders, established coronary heart disease or other cardiac conditions, which could determine sudden death
- Attempted suicide or suicidal ideation
- Drugs of abuse or substance use disorder
- A significant illness or infection requiring medical treatment in the past 30 days.
- Untreated narrow angle glaucoma.
- Women who are pregnant or nursing.
- Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, or monoamine oxidase inhibitors (MAOI) or linezolid within 14 days of the start of treatment, allergies to sulfonamides.
- Diabetes with unstable glucose control in the past 15 days.
- > 500 mg/day of Aspirin
- Low sodium or potassium.
- Any condition that in the investigator's opinion would present an unreasonable risk to the participant.
- History of using oral or nasal devices (such as mandibular advancement devices) for the treatment of OSA may enroll as long as the devices are not used during participation in the study for at least 2 weeks prior to study begin.
- History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study.
- Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.
- Patient currently receiving: MAOIs, Serotonin and Norepinephrine Reuptake Inhibitors, Norepinephrine Reuptake Inhibitors, Lithium, Tricyclic antidepressants, strong CYP2D6 inhibitors, other strong inhibitors cytochrome P450, thiazides diuretics, benzodiazepines, opioids, drugs with clinically significant cardiac QT-interval prolonging effects, drugs known to lower seizure threshold, amphetamines, antiepileptics, modafinil or armodafinil, beta2 agonists, antipsychotics, pseudoephedrine, phenylephrine, oxymetazoline, drugs for Parkinson's, Alzheimer's, Huntington's, Amyotrophic Lateral Sclerosis, or drugs for other neurodegenerative diseases, more than 500 mg/day of Aspirin or salicylates, sodium Phosphate.
- Known hypersensitivity to study drugs
Sites / Locations
- Istituto Auxologico Italiano,Ospedale San LucaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AD981
Placebo
Arm Description
AD981
Placebo
Outcomes
Primary Outcome Measures
Nocturnal transcutaneous CO2 pressure (PtcCO2)
Secondary Outcome Measures
Proportion of participants without nocturnal hypoventilation
Apnea-Hypopnea Index (AHI)
Full Information
NCT ID
NCT05448443
First Posted
July 1, 2022
Last Updated
October 5, 2023
Sponsor
Istituto Auxologico Italiano
Collaborators
Apnimed Inc., VIS Ethic Research Srl, University of Florence, STM Pharma PRO srl
1. Study Identification
Unique Protocol Identification Number
NCT05448443
Brief Title
Study of AD981 Versus Placebo in Obesity Hypoventilation Syndrome
Acronym
ATOHS
Official Title
Crossover, Double-blind, Phase 2 Study of AD981 Versus Placebo in Obesity Hypoventilation Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 21, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Istituto Auxologico Italiano
Collaborators
Apnimed Inc., VIS Ethic Research Srl, University of Florence, STM Pharma PRO srl
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a randomized, double blind, placebo-controlled, cross-over, phase II, single center efficacy study of AD981 in patients with obesity hypoventilation syndrome documented by polysomnography (PSG) and transcutaneous, overnight measurement of CO2 (PtcCO2).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity Hypoventilation Syndrome (OHS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Patients who meet the eligibility criteria will be randomized equally to receive AD981 or matching placebo.
After 14 days of treatment and a washout period, the patients crossover to the other treatment arm for 14 days.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AD981
Arm Type
Experimental
Arm Description
AD981
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
AD981
Intervention Description
Oral administration of AD981 in the morning and before sleep for 14 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Oral administration of placebo in the morning and before sleep for 14 days
Primary Outcome Measure Information:
Title
Nocturnal transcutaneous CO2 pressure (PtcCO2)
Time Frame
From baseline to the last day of treatment (14 days after the start of each treatment period)
Secondary Outcome Measure Information:
Title
Proportion of participants without nocturnal hypoventilation
Time Frame
From baseline to the last day of treatment (14 days after the start of each treatment period)
Title
Apnea-Hypopnea Index (AHI)
Time Frame
From baseline to the last day of treatment (14 days after the start of each treatment period)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be able to understand the nature of the study and sign the informed consent
BMI > 35 kg/m2 and presence of nocturnal hypoventilation
Previous surgical treatment for OSA is allowed if ≥ 1 year prior to enrollment
If in treatment, CPAP or BPAP or mandibular advancement device or positional therapy intolerance or poor compliance
Exclusion Criteria:
Narcolepsy, craniofacial malformation, renal failure, hepatic disease, schizophrenia, schizoaffective disorder or bipolar disorder, cognitive dysfunction, severe neurological disorder, pheochromocytoma, adrenocortical insufficiency, hyperchloremic acidosis.
Respiratory (COPD, ILD, oxygen therapy) or cardiac (Heart Failure, Atrial fibrillation, established severe peripheral arterial disease) disease or hypertension requiring more than 3 medications for control
Cardiomyopathies, heart malformation or structural heart alterations, severe rhythm disorders, established coronary heart disease or other cardiac conditions, which could determine sudden death
Attempted suicide or suicidal ideation
Drugs of abuse or substance use disorder
A significant illness or infection requiring medical treatment in the past 30 days.
Untreated narrow angle glaucoma.
Women who are pregnant or nursing.
Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, or monoamine oxidase inhibitors (MAOI) or linezolid within 14 days of the start of treatment, allergies to sulfonamides.
Diabetes with unstable glucose control in the past 15 days.
> 500 mg/day of Aspirin
Low sodium or potassium.
Any condition that in the investigator's opinion would present an unreasonable risk to the participant.
History of using oral or nasal devices (such as mandibular advancement devices) for the treatment of OSA may enroll as long as the devices are not used during participation in the study for at least 2 weeks prior to study begin.
History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study.
Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.
Patient currently receiving: MAOIs, Serotonin and Norepinephrine Reuptake Inhibitors, Norepinephrine Reuptake Inhibitors, Lithium, Tricyclic antidepressants, strong CYP2D6 inhibitors, other strong inhibitors cytochrome P450, thiazides diuretics, benzodiazepines, opioids, drugs with clinically significant cardiac QT-interval prolonging effects, drugs known to lower seizure threshold, amphetamines, antiepileptics, modafinil or armodafinil, beta2 agonists, antipsychotics, pseudoephedrine, phenylephrine, oxymetazoline, drugs for Parkinson's, Alzheimer's, Huntington's, Amyotrophic Lateral Sclerosis, or drugs for other neurodegenerative diseases, more than 500 mg/day of Aspirin or salicylates, sodium Phosphate.
Known hypersensitivity to study drugs
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elisa Perger, MD
Phone
+390261911
Ext
2705
Email
e.perger@auxologico.it
First Name & Middle Initial & Last Name or Official Title & Degree
Luca Grappiolo
Phone
+390261911
Ext
2894
Email
luca.grappiolo@auxologico.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elisa Perger, MD
Organizational Affiliation
Istituto Auxologico Italiano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Istituto Auxologico Italiano,Ospedale San Luca
City
Milano
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisa Perger, MD
Phone
+390261911
Ext
2705
Email
e.perger@auxologico.it
First Name & Middle Initial & Last Name & Degree
Elisa Perger, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of AD981 Versus Placebo in Obesity Hypoventilation Syndrome
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