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Trial registered on ANZCTR


Registration number
ACTRN12621000809831
Ethics application status
Approved
Date submitted
24/02/2021
Date registered
25/06/2021
Date last updated
12/05/2022
Date data sharing statement initially provided
25/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
An Open Label Extension on the Examination of the Combination of Dronabinol and Acetazolamide for Treatment of Obstructive Sleep Apnoea (OSA)
Scientific title
An Open Label Extension study investigating the effect of dronabinol combined with acetazolamide administered for 6 months, on Apnoea Hypopnea Index (AHI) in adults with obstructive sleep apnoea (OSA)
Secondary ID [1] 302870 0
IHLOSAOLE1
Universal Trial Number (UTN)
Trial acronym
IHLOSAOLE1
Linked study record
The trial ACTRN12620000916943, the Dose Finding crossover trial investigating the effect of dronabinol combined with acetazolamide on AHI in adults with OSA, is the initial trial to which this IHLOSAOLE1 trial is the open label extension to, allowing participants that benefitted from the investigational product and had a reduction of the sleep apnoea symptoms can to continue taking the investigational product for another 6 months.

Health condition
Health condition(s) or problem(s) studied:
Obstructive Sleep Apnoea 319870 0
Condition category
Condition code
Respiratory 317809 317809 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is linked to the IHLOSAPOC1-Dose finding crossover trial investigating the effect of dronabinol combined with acetazolamide on Apnoea Hypopnea Index (AHI) in adults with obstructive sleep apnoea (OSA);ACTRN126200000916943.
This study will determine the therapeutic benefit of a combination of dronabinol and acetazolamide at reducing AHI in adults with obstructive sleep apnoea over a 6 month period in participants that completed the proof of concept study, IHLOSAPOC1. There is no requirement for participants to washout before commencing the open label extension study, once completing the initial proof of concept study.
Investigational product will be administered by mouth as two separate capsules. Participants will be provided with a blister pack containing the investigational product at the start of each 28 day period. Each blister will contain a single dose, one dronabinol and one acetazolamide capsule, of the investigational product. Participants will continuously self-administer the investigational product for the entire 6 month period. Participants will collect 28 day pack of investigational product at each clinic visit. There are a total of 28 doses, one per day, over a 28 day treatment period. They will be required to return the used/empty drug pack at each clinic visit to monitor adherance to the daily dosing schedule and for drug compliance review. The doses will be administered approximately 60 min before bedtime each night.
The dosing will commence with the lowest dose, as defined in IHLOSAPOC1, low (2.5 mg dronabinol 125 mg acetazolamide). If the drug combination is not effective at reducing the sleep apnoea symptoms in a participant, as determined by the patient reported outcomes and AHI measured at each PSG, the dose may be increased to the medium dose, medium (5 mg dronabinol 250 mg acetazolamide) at the discretion of the investigator. The total treatment period is 24 weeks (6 months).
Intervention code [1] 319162 0
Treatment: Drugs
Comparator / control treatment
This is an open label study and hence no comparator will be used.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326624 0
Apnoea Hypopnoea Index (AHI) as measured by overnight polysomnography over 6 months treatment with dronabinol and acetazolamide.
Timepoint [1] 326624 0
Polysomnography (PSG), a total of three at Day 28, Day 84 and Day 168 to assess the Apnoea Hypopnoea Index (AHI) at each of these timepoints.
Secondary outcome [1] 392169 0
Change in Oxygen Desaturation Index (ODI) index as assessed by Polysomnography upon treatment with dronabinol and acetazolamide after 1, 3 and 6 months,
Timepoint [1] 392169 0
Polysomnography at 1 month, 3 months and 6 months to assess the Oxygen Desaturation Index (ODI) at these timepoints.
Secondary outcome [2] 392170 0
Change in alertness upon treatment with dronabinol and acetazolamide after 1, 3 and 6 months, as assessed by patient reported outcomes as captured in the questionnaire Stanford Sleepiness Scale.
Timepoint [2] 392170 0
1 month post dosing of investigational product (Day 1), 3 months post dosing of investigational product (Day 84) and 6 months post dosing of investigational product (Day 168).
Secondary outcome [3] 392171 0
Change in daytime somnolence upon treatment with dronabinol and acetazolamide after 1, 3 and 6 months as assessed by patient reported outcomes as captured in the questionnaire Epworth Sleepiness Scale.
Timepoint [3] 392171 0
1 month post dosing of investigational product (Day 1), 3 months post dosing of investigational product (Day 84) and 6 months post dosing of investigational product (Day 168).
Secondary outcome [4] 392172 0
Change in mood as assessed by Profile Of Mood State-2 (POMS-2) questionnaire upon treatment with dronabinol and acetazolamide after 1, 3 and 6 months
Timepoint [4] 392172 0
1 month post dosing of investigational product (Day 1), 3 months post dosing of investigational product (Day 84) and 6 months post dosing of investigational product (Day 168).
Secondary outcome [5] 392173 0
Change in well-being as assessed by 36 item short form survey instrument SF-36, upon treatment with dronabinol and acetazolamide after 1, 3 and 6 months
Timepoint [5] 392173 0
1 month post dosing of investigational product (Day 1), 3 months post dosing of investigational product (Day 84) and 6 months post dosing of investigational product (Day 168).
Secondary outcome [6] 392174 0
To investigate the clearance of THC from the system as assessed by urine drug screening test by the morning post dose after 1, 3 and 6 month treatment.
Timepoint [6] 392174 0
1 month post dosing of investigational product (Day 1), 3 months post dosing of investigational product (Day 84) and 6 months post dosing of investigational product (Day 168).
Secondary outcome [7] 392175 0
For epilepsy participants, change in seizure frequency upon treatment with dronabinol and acetazolamide after 1, 3 and 6 months compared to the 7 day treatment periods in the proof of concept study. All seizure frequency and type will be captured in the seizure diary.
Timepoint [7] 392175 0
1 month post dosing of investigational product (Day 1), 3 months post dosing of investigational product (Day 84) and 6 months post dosing of investigational product (Day 168).
Secondary outcome [8] 397017 0
Monitoring of Adverse Events will be recorded throughout the trial and coded using the current version of the Medical Dictionary of Regulatory Activities (MedDRA)
Timepoint [8] 397017 0
Adverse events to be recorded at each visit starting 1 month post dosing of investigational product (Day 1), Days 28, 56, 84, 112, 140, 168, 173 (6 months post-dosing of investigational product) with coding to occur during statistical analysis of data at the end of the study.
Secondary outcome [9] 397096 0
Blood sampling and analysis to monitor possible effects of the investigational product on electrolyte and liver enzymes levels at screening, Day 1, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168 and end of study (days-173-178)
Timepoint [9] 397096 0
Electrolyte and liver enzymes to be compared and assessed from blood sampling taken at screening, Day 1, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168 and end of study (days-173-178)
Secondary outcome [10] 397097 0
Monitor dosing compliance from Day 1, Day 28, Day 56, Day 84, Day 112, Day 140, Day 168 and end of study(Day 173-178)
Timepoint [10] 397097 0
Review drug accountability post each treatment period Day 28, Day 56, Day 84, Day 112, Day 140, Day 168 and end of study (Day 173-178)

Eligibility
Key inclusion criteria
Linked study record ACTRN126200009116943
1.Participants must have completed participation in the IHLOSAPOC1 study (ACTRN126200009116943) and had a reduction in AHI upon treatment with dronabinol and acetazolamide
2.Would benefit from continued treatment with dronabinol and acetazolamide at the discretion of the treating physician and principal investigator
3.No known allergic reaction to cannabis products with previous use
4.No known allergic reaction to sesame (dronabinol is formulated in sesame oi)
5.No known allergy to acetazolamide or other sulphonamides
6.Ability to speak and read English
7.Agree to refrain from driving for the duration of the study
8.Have no history of past substance abuse (within the past 5 years) or current abuse of illicit drugs (within 6 months) other than the dronabinol used in IHLOSAPOC1
9.Physically well, based on the opinion of the investigator, with no severe psychiatric, cardiac, renal, endocrine, gastrointestinal, or bleeding disorders
10.If male, agree to be sexually abstinent or agree to use two approved methods of contraception when engaging in sexual activity from study visit 1 through to the end of the study. Subjects must agree to use two approved methods of contraception for 10 days following the last administration of the study drug, and not donate sperm during this same period of time. In the event that the sexual partner is surgically sterile, contraception is not necessary.
o Approved methods of contraception;
a. Inter-uterine device (IUD) in place for at least 3 months prior to Day 1 through 10 days following the final dosing of the study drug
b. Barrier method (Condom or diaphragm) for at least 14 days prior to Visit 1 through to 10 days following the last administration of the study drug.
c. Stable hormonal contraceptive for at least 3 months prior to Visit 1 and barrier method (condom or diaphragm) for at least 14 days prior to Visit 1 through to 10 days following the last administration of the study drug.
d. Surgical sterilization (vasectomy) at least 6 months prior to Visit 1.
Females of non-childbearing potential who have established serum FSH levels >40mlU/ml (i.e. determined prior to this study and not an assessment performed as part of this study) are either postmenopausal or have undergone one of the following sterilization procedures at least 6 months prior to Visit 1;
o Bilateral tubal ligation
o Hysterectomy
o Hysterectomy with unilateral or bilateral oophorectomy
o Bilateral oophorectomy

11. Females of childbearing potential that are not currently pregnant or lactating
12. Not taking any vitamins, herbal remedies or supplements within 5 days of admission
13. Voluntarily consent to participate in the study and complete all study required tasks, as instructed by the protocol, including the completion of questionnaires and diaries
14. High (>15) score on the Epworth Sleepiness Scale
15. Willing and able to self-administer two capsules by mouth, 60 minutes before bedtime, each night for the duration of the trial (24 weeks).
Minimum age
21 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Linked study record ACTRN126200009116943
1. AHI of < 15
2. Diagnosis of sleep disorder other than sleep apnoea (e.g. restless legs syndrome, narcolepsy, parasomnias etc.)
3. Currently using a positive airway pressure device (e.g. CPAP, VPAP), or other treatment for OSA including mandibular advancement splint, or positional device
4. BMI > 45
5. ESS < 7 (excludes non-sleepy participants)
6. Inability to speak or read English
7. Pregnant or breast-feeding
8. History of drug or substance abuse (within the last 5 years) or current illicit drug abuse (with in the last 6 months)
9. Not physically well, or a history of severe psychiatric, cardiac, endocrine, renal, gastrointestinal, or bleeding disorders
10. Currently taking medication (except for prophylactic antibiotics, contraceptive pill or other routine medications to treat benign conditions, such as antibiotics to treat acne)
11. History of known conditions to include the following; hypokalemia (low blood potassium), hyponatremia (low blood sodium), hypochloremia acidosis, adrenal insufficiency, impaired kidney function, marked liver disease or impaired liver function or abnormal blood cell counts, within the last 6 months.
12. Current participation in any other trials involving investigational or marketed products within 30 days prior to the screening visit with the exception of the proof-of-concept study IHLOSAPOC1 (Linked study record ACTRN126200009116943)
13. If there are any additional concerns about the subject’s safety or well-being as a result of participating in the trial, subjects can be excluded at the treating physician’s discretion.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
NA
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
This study is linked to ACTRN12620000916943 and hence data will be analysed similarly. All statistical tests will be performed two tailed at the 5% significance level and performed using IBM SPSS statistical package. Z scores for the distribution will be calculated for each variable and displayed in histogram form. Out of range values will be recoded as missing values.
Results for the PSG (AHI) and from the sleep quality/ length/ well-being measures will also be compared using a mixed design analysis of covariance (MANCOVA), with treatment (placebo, low, medium, high dose) as the between-subject variable, time as the within-subjects variable, and baseline score as the covariate. The maximum number of participants included in the analysis is 12 however this is dependent on how many participants consent to continue into this study.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/07/2021
Actual
10/08/2021
Date of last participant enrolment
Anticipated
31/12/2021
Actual
10/08/2021
Date of last data collection
Anticipated
31/01/2022
Actual
15/02/2022
Sample size
Target
12
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 19670 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 33261 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 307286 0
Commercial sector/Industry
Name [1] 307286 0
Incannex Healthcare Ltd
Country [1] 307286 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Incannex Healthcare Ltd
Address
Unit 207, 11 Solent Circuit
Norwest, 2153
New South Wales
Country
Australia
Secondary sponsor category [1] 308687 0
None
Name [1] 308687 0
Address [1] 308687 0
Country [1] 308687 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307384 0
Alfred Human Research Ethics Committee
Ethics committee address [1] 307384 0
55 Commercial Rd,
Melbourne VIC 3004
Ethics committee country [1] 307384 0
Australia
Date submitted for ethics approval [1] 307384 0
06/01/2021
Approval date [1] 307384 0
19/07/2021
Ethics approval number [1] 307384 0

Summary
Brief summary
Participants that have completed all study visits on Linked study: ACTRN 12620000916943, (Dose finding crossover trial investigating the effect of dronabinol combined with acetazolamide on Apnoea Hypopnea Index (AHI) in adults with obstructive sleep apnoea (OSA)) AND have an overall reduction in the Apnoea Hypopnoea Index (AHI) will be granted the option to participate in the IHLOSAOLE1 study.
This will enable participants who had an overall reduction in OSA to continue to take the investigational product for a further 6 months (24 weeks). The participants will complete PSGs at the sleep clinic, Sleepiness, mood and quality of life questionnaires AHI, daytime somnolence, mood and quality of life scores will be compared to baseline to observe if efficacy is maintained over the 6 month period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107042 0
Prof Terence O'brien
Address 107042 0
Department of Neurosciences
4th Floor, Centre Block
The Alfred Hospital
55 Commerical Road
Melbourne VIC 3004
Country 107042 0
Australia
Phone 107042 0
+61 3 9903 0855
Fax 107042 0
Email 107042 0
[email protected]
Contact person for public queries
Name 107043 0
Jack Germaine
Address 107043 0
Epilepsy Research Unit – 4 Centre Block, Level 4
The Alfred Hospital
55 Commercial Rd,
Melbourne VIC 3004
Country 107043 0
Australia
Phone 107043 0
+61 3 9076 2029
Fax 107043 0
Email 107043 0
[email protected]
Contact person for scientific queries
Name 107044 0
Terence O'Brien
Address 107044 0
Department of Neurosciences
4th Floor, Centre Block
The Alfred Hospital
55 Commerical Road
Melbourne VIC 3004
Country 107044 0
Australia
Phone 107044 0
+61 3 9903 0855
Fax 107044 0
Email 107044 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data will be commercially sensitive


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.