Study for Efficacy and Dose Escalation of AD313 + Atomoxetine (SEED)

NCT05101122 | Completed Phase 1 Results FDA Drug

• 1 other identifier: SEED
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

The SEED study is designed to assess the safety and efficacy for Obstructive Sleep Apnea (OSA) of 3 escalating dose combinations of atomoxetine with AD313 compared to baseline and to atomoxetine alone.

Conditions

Obstructive Sleep Apnea

Keywords

Apnea, Obstructive Sleep; Sleep Apnea Syndromes; Upper Airway Reistance Syndrome

Outcome Measures

Primary Outcomes (1)

• Apnea-Hypopnea Index (AHI)4% Events Per Hour

  Compares high dose atomoxetine (80/10) versus baseline

  28 days

Study Arms (2)

Dosing Period 1: Atomoxetine

ACTIVE COMPARATOR

3 days of atomoxetine 40 mg followed by 4 days of atomoxetine 80 mg.

Drug: Dosing 1: Atomoxetine

Dosing Period 2-4: AD313

EXPERIMENTAL

Week 2: atomoxetine 40 mg/dronabinol 2.5 mg Week 3: atomoxetine 80 mg/dronabinol 5 mg Week 4: atomoxetine 80 mg/dronabinol 10 mg

Drug: AD313

Interventions

Dosing 1: Atomoxetine DRUG

Oral administration at bedtime

Also known as: 40mg or 80 mg Atomoxetine

Dosing Period 1: Atomoxetine

AD313 DRUG

Escalating dose of AD313; Oral administration at bedtime

Also known as: atomoxetine dronabinol

Dosing Period 2-4: AD313

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age and Sex
• to 65 years of age, inclusive, at the Screening Visit. Disease Measures
• AHI 10 to 50 (hypopneas defined by 4% oxygen desaturation)
• ≤25% of apneas are central or mixed apneas at V2 baseline PSG Weight
• BMI between 18.5 and 40.0 kg/m2, inclusive, at the pre-PSG visit.
• Male participants:
• If male and sexually active with female partner(s) of childbearing potential, participant must agree, from Study Day 1 through 1 week after the last dose of study drug, to practice the protocol specified contraception (see Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information).
• Female participants:
• If a woman of childbearing potential (WOCBP), the participant must agree, from Study Day 1 through 1 week after the last dose of study drug, to practice the protocol specified contraception (See Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information). All WOCBP must have negative result of a serum pregnancy test performed at screening.
• If female and of non-childbearing potential, the participant must be either postmenopausal (defined as age ≥ 55 years with no menses for 12 or more months without an alternative medical cause) or permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• Informed Consent
• Participant voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)-approved informed consent prior to performing any of the Screening Visit procedures.
• Participant must be able to understand the nature of the study and must have the opportunity to have any questions answered.

You may not qualify if:

• Medical Conditions
• History of clinically significant sleep disorder other than OSA.
• Clinically significant craniofacial malformation.
• Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery disease or cardiac failure) or hypertension requiring more than 2 medications for control (combination medications are considered as 1 medication for this purpose).
• Clinically significant neurological disorder, including epilepsy/convulsions.
• History of schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM 5) or International Classification of Disease tenth edition criteria.
• History of attempted suicide within 1 year prior to screening, or current suicidal ideation.
• Medically unexplained positive screen for drugs of abuse or history of substance use disorder as defined in DSM-V within 24 months prior to Screening Visit.
• A significant illness or infection requiring medical treatment in the past 30 days.
• Clinically significant cognitive dysfunction as determined by investigator.
• Women who are pregnant or nursing. Prior/Concomitant Therapy
• History of using devices for OSA treatment, including CPAP, oral or nasal devices, or positional devices, may enroll as long as the devices have not been used for at least 2 weeks prior to first study visit and are not used during participation in the study.
• History of chronic oxygen therapy.
• Use of medications from the list of disallowed concomitant medications.
• Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, strong cytochrome P450 2D6 (CYP2D6) inhibitors, or monoamine oxidase inhibitors (MAOI) within 14 days of the start of treatment, or concomitant with treatment.

Sponsors & Collaborators

• Apnimed: lead

Study Sites (2)

Santa Monica Clinical Trials

Los Angeles, California, 90025, United States

Location

Clayton Sleep Institute

St Louis, Missouri, 63143, United States

Location

Related Publications (1)

• Messineo L, Norman D, Ojile J. The combination of atomoxetine and dronabinol for the treatment of obstructive sleep apnea: a dose-escalating, open-label trial. J Clin Sleep Med. 2023 Jul 1;19(7):1183-1190. doi: 10.5664/jcsm.10528.

  PMID: 36805833 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea Syndromes

Interventions

Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Clinical Trials
• Organization: Apnimed

clinicaltrials@apnimed.com

6015008880

Study Officials

• Ron Farkas, MD, PhD

  Apnimed Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: November 1, 2021
• Study Start: October 19, 2021
• Primary Completion: April 18, 2022
• Study Completion: April 18, 2022
• Last Updated: April 7, 2023
• Results First Posted: April 7, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)