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

NCT ID: NCT05101122

Last Updated: 2023-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-19
• Study Completion Date: 2022-04-18

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.

Detailed Description

The SEED study is an open-label, 4 consecutive period dose-escalation study of combinations of AD313 vs. atomoxetine alone in participants with moderate- to severe OSA. A screening polysomnogram (PSG) will be conducted to establish that each participant meets study enrollment criteria and to serve as baseline. Each participant will then receive escalating doses of AD313 with on-drug PSGs to be conducted on the final night of dosing.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dosing Period 1: Atomoxetine

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

Group Type: ACTIVE_COMPARATOR

Dosing 1: Atomoxetine

Intervention Type: DRUG

Oral administration at bedtime

Dosing Period 2-4: AD313

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

Group Type: EXPERIMENTAL

AD313

Intervention Type: DRUG

Escalating dose of AD313; Oral administration at bedtime

Interventions

Dosing 1: Atomoxetine

Oral administration at bedtime

Intervention Type: DRUG

AD313

Escalating dose of AD313; Oral administration at bedtime

Intervention Type: DRUG

Other Intervention Names

40mg or 80 mg Atomoxetine; atomoxetine dronabinol

Eligibility Criteria

Inclusion Criteria

Age and Sex

1. 25 to 65 years of age, inclusive, at the Screening Visit. Disease Measures

2. AHI 10 to 50 (hypopneas defined by 4% oxygen desaturation)

3. ≤25% of apneas are central or mixed apneas at V2 baseline PSG Weight

4. BMI between 18.5 and 40.0 kg/m2, inclusive, at the pre-PSG visit.

Male participants:

5. 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:

6. 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.

7. 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

8. 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.

9. Participant must be able to understand the nature of the study and must have the opportunity to have any questions answered.

Exclusion Criteria

Medical Conditions

1. History of clinically significant sleep disorder other than OSA.

2. Clinically significant craniofacial malformation.

3. 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).

4. Clinically significant neurological disorder, including epilepsy/convulsions.

5. 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.

6. History of attempted suicide within 1 year prior to screening, or current suicidal ideation.

7. 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.

8. A significant illness or infection requiring medical treatment in the past 30 days.

9. Clinically significant cognitive dysfunction as determined by investigator.

10. Women who are pregnant or nursing. Prior/Concomitant Therapy

11. 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.

12. History of chronic oxygen therapy.

13. Use of medications from the list of disallowed concomitant medications.

14. 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.

Prior/Concurrent Clinical Study Experience

15. Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.

Diagnostic Assessments

16. Hepatic transaminases >2X the upper limit of normal (ULN), total bilirubin >1.5X ULN (unless confirmed Gilbert syndrome), estimated glomerular filtration rate < 60 ml/min.

17. PLM arousal index >15 Other Exclusions

18. <5 hours typical sleep duration.

19. ESS > 18

20. Night- or shift-work sleep schedule which causes the major sleep period to be during the day.

21. Employment as a commercial driver or operator of heavy or hazardous equipment.

22. Typically smoking more than 10 cigarettes or 2 cigars per day, or inability to abstain from smoking during overnight PSG visits.

23. Unwilling to use specified contraception.

24. History of regular alcohol consumption of more than 14 standard units per week (males) or more than 7 standard units per week (females), or unwillingness to limit alcohol consumption to no greater than 2 units/day (males), 1 unit per day (females), not to be consumed within 3 hours of bedtime or on PSG nights.

25. Unwilling to limit during the study period caffeinated beverage intake (e.g., coffee, cola, tea) to 400 mg/day or less of caffeine, not to be used within 3 hours of bedtime.

26. Any condition that in the investigator's opinion would present an unreasonable risk to the participant, or which would interfere with their participation in the study or confound study interpretation.

27. Participant considered by the investigator, for any reason, an unsuitable candidate to receive atomoxetine and/or dronabinol or unable or unlikely to understand or comply with the dosing schedule or study evaluations.

Meals and Dietary Restrictions

1. Participants should refrain from consumption of any nutrients known to modulate CYP enzyme activity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, pomegranate, and Seville or Moro [blood] orange products) within 72 hours before the first dose of study drug and during the study.

2. Diet should be generally stable during the study, e.g., new diet programs should not be initiated.

Caffeine, Alcohol, and Tobacco

1. During the outpatient portions of the study, participants should refrain from more than 2 standard units per day of alcohol for men or 1 unit/day for women, consumed no less than 3 hours prior to bedtime. Alcohol should not be consumed on PSG nights.

2. Moderate consumption of caffeinated beverages, containing up to a total of 400 mg caffeine per day, is permitted during the study period, consumed no less than 3 hours prior to bedtime.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Apnimed

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ron Farkas, MD, PhD

Role: STUDY_DIRECTOR

Apnimed Inc.

Locations

Clayton Sleep Institute

St Louis, Missouri, United States

Santa Monica Clinical Trials

Los Angeles, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36805833 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

SEED

Identifier Type: -

Identifier Source: org_study_id