Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001365853
Ethics application status
Approved
Date submitted
13/08/2021
Date registered
8/10/2021
Date last updated
17/05/2022
Date data sharing statement initially provided
8/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of RLS103 (CBD-Technosphere® Inhalation Powder) in Healthy Adult Volunteers
Scientific title
A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of RLS103 (CBD-Technosphere® Inhalation Powder) in Healthy Adult Volunteers
Secondary ID [1] 304787 0
RC2021-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Panic Disorder 322848 0
Social Anxiety Disorder 322849 0
Condition category
Condition code
Mental Health 320428 320428 0 0
Anxiety

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cannabidiol Inhalation Powder, is a dry powder product comprising Cannabidiol and the inhalation excipients fumaryl diketopiperazine and 1,2 distearoyl sn glycero-3-phosphocholine, filled into cartridges for administration by oral inhalation through the DreamboatTM inhaler
The RLS103 is a drug/device combination consisting of single-use cartridges filled with a dry powder for inhalation and a breath-powered inhaler. When the participant inhales through the device, the powder is aerosolized and delivered to the lungs.

The study consists of total 3 cohorts. A total of 30 participants will be sequentially assigned to 1 of 3 cohorts (10 participants per cohort). Each cohort have 4 treatment periods with a washout period of 7 days between each treatment within a cohort. The Cohorts will be conducted one after the other, starting with cohort 1. A cohort may overlap with treatment periods with smaller doses in a previous cohort

Three different formulations (20% CBD, 28% CBD and 35% CBD). One formulation will be tested in each cohort. Thus participants in Cohort 1 will receive the 20% formulation in escalating amounts; and participants in Cohorts 2 and 3 will receive the 28% and 35% formulations, respectively.



Cohort 1 includes:
- Treatment period 1: 2 mg, single cartridge of orally inhaled RLS103
- Treatment period 2: 3 mg, single cartridge of orally inhaled RLS103
- Treatment period 3: 4 mg. single cartridge of orally inhaled RLS103
- Treatment period 4: 8 mg, 2 cartridges, 1 immediately after the other, of orally inhaled RLS103
For Cohort 1 only, a sentinel dosing approach will be taken in each Treatment Period so that 4 participants will be dosed initially and, if there are no safety concerns in the 48 hours post dose, the remaining 6 participants will then be dosed.

Cohort 2 includes:
- Treatment period 1: 2 mg, single cartridge of orally inhaled RLS103
- Treatment period 2: 4.2 mg, single cartridge of orally inhaled RLS103
- Treatment period 3: 5.6 mg, single cartridge of orally inhaled RLS103
- Treatment period 4: 11.2 mg, 2 cartridges, 1 immediately after the other, of orally inhaled RLS103

Cohort 3 includes:
- Treatment period 1: 2 mg, single cartridge of orally inhaled RLS103
- Treatment period 2: 4.2 mg, single cartridge of orally inhaled RLS103
- Treatment period 3: 5.6 mg, single cartridge of orally inhaled RLS103
- Treatment period 4: 11.2 mg, 2 cartridges, 1 immediately after the other, of orally inhaled RLS103

In treatment periods 1, 2, and 3 in each Cohort, participants will receive a single cartridge of orally inhaled RLS103 and in treatment period 4 in each cohort, participants will receive 2 cartridges, 1 immediately after the other, of orally inhaled RLS103.

Each cartridge will be weighed before and after inhalation to quantify the amount of powder inhaled by each participant in each treatment in each cohort.

Duration for each participant is up to 38 days plus or minus 2 days at End Of Study.


Intervention code [1] 321174 0
Treatment: Drugs
Intervention code [2] 321175 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328273 0
To assess the safety and tolerability of single ascending doses of RLS103 in healthy adult volunteers
To be assessed by monitoring
- incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-related TEAEs as assessed through Common Terminology Criteria for Adverse Events (CTCAE) v5.0
- Clinical laboratory results (includes hematology, serum chemistry, and urinalysis)
- Vital signs (Systolic and diastolic blood pressure, respiratory rate, pulse rate, and body temperature)
- Physical examination (includes general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes)
- Spirometry measurement (assessed by Forced Expiratory Volume (FEV1), Forced Vital Capacity (FVC) and FEV1/FVC ratio.
Timepoint [1] 328273 0
From Baseline to Day 1, Day 7, Day 8, Day 14, Day 15, Day 21, Day 22 post-first dose
Secondary outcome [1] 398349 0
To evaluate the pharmacokinetics (PK) of 3 different formulations of RLS103 including dose linearity across and between formulations
Pharmacokinetics parameter includes:
- Tmax (time to maximum concentration)
- Cmax (maximum concentration)
- AUC0-t (area under the time concentration curve from time zero to time t)
- AUC0-inf (AUC from time zero to infinity)
- Kel (elimination rate constant)
- t½ (elimination half-life)
- CL/F (apparent total clearance)
- Vz/F (apparent volume of distribution)

Blood sample collected for pharmacokinetic assessment
Timepoint [1] 398349 0
Blood samples for PK assessment will be collected at pre-dose and 2, 4 and 6 minutes (±1 minute) post dose, at 10, 15, 30, and 45 minutes (±5 minutes) post dose, and at 1, 1.5, 2, 4, 8, and 12 hours (±15 minutes) post dose on Day 1, Day 8, Day 15 and Day 22 post-first dose

Eligibility
Key inclusion criteria
1. Healthy male or female volunteers, between 18 and 55 years of age, inclusive at the time of informed consent.
2. In good health as determined by past medical history, physical examination, vital signs, ECG, and clinical laboratory tests at Screening. Continued participation in each subsequent treatment period will be at the discretion of Investigator upon review of ongoing safety and compliance assessments.
3. BMI between 18 and 32 kg/m2 (inclusive) with a body weight greater than or equal to 50 kg.
4. Non-smoker (cigarettes, cigars, e-cigarettes, or nicotine containing products in the 6 months prior to Screening) as confirmed by negative cotinine results (less than 10 ng/mL) at Screening and must be willing to abstain from smoking for the duration of the study.
5. Must have no medical contraindication to CBD, including known allergies or hypersensitivities to CBD or the excipients in Cannabidiol Inhalation Powder.
6. Must demonstrate the ability to use the inhaler correctly through a training tool (BluHale) and must be able to tolerate inhalation of a placebo powder.
7. Females must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception from Screening until study completion, including the follow up period. Double contraception is defined as a condom AND one other form of the following:
a. Established hormonal contraception (including oral contraceptive pills [OCPs] long acting implantable hormones and injectable hormones) for at least 1 month prior to Screening.
b. A vaginal ring or an intrauterine device (IUD).
c. Documented evidence of surgical sterilization at least 6 months prior to Screening (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) for women or vasectomy at least 90 days prior to Screening for men (with appropriate post-vasectomy documentation of the absence of sperm in semen), provided the male partner is a sole partner.
Women not of childbearing potential must be postmenopausal for greater than or equal to 12 months. Postmenopausal status will be confirmed through testing of follicle stimulating hormone (FSH) levels greater than or equal to 40 IU/L at Screening for amenorrhoeic female participants. Females who are abstinent from heterosexual intercourse will also be eligible.
Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not considered highly effective methods of birth control. Participant complete abstinence for the duration of the study and for 1 month after the last study treatment is acceptable.
All women that are not postmenopausal must have a negative pregnancy test at Screening and Day -1 and be willing to have additional pregnancy tests as required throughout the study.
Female participants who are in same sex relationships are not required to use contraception.
Males must be surgically sterile (more than 90 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from Screening until study completion, including the follow-up period. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner that includes: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring, or an IUD. Participants with same sex partners (abstinence from penile-vaginal intercourse) are eligible when this is their preferred and usual lifestyle.
Males must not donate sperm for at least 90 days after the last dose of study drug.
8. Must have the ability and willingness to attend the necessary visits to the CRU.
9. Must sign an informed consent form (ICF) indicating that they understand the purpose of the study and the procedures required for the study and are willing to participate in the study.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
2. Currently using marijuana, marijuana cigarettes, cannabis-related products, or CBD; or have used any of these products within 3 weeks prior to Screening.
3. History of or current clinically significant medical illness including but not limited to, cardiac arrhythmias or other cardiac disease; vascular disease; hematologic disease; coagulation disorders (including any abnormal bleeding or blood dyscrasias); lipid abnormalities; any pulmonary disease, including bronchospastic respiratory disease, or chronic obstructive pulmonary disease [COPD]; diabetes mellitus; hepatic or renal insufficiency (creatinine clearance below 60 mL/min per the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]); thyroid disease; neurologic (including epilepsy) or psychiatric disease, current infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results.
4. Use of prescription or nonprescription medications, including vitamins or herbal supplements, within 7 days of Day 1 and until EOS (excluding hormonal contraceptives and acetaminophen, which are not expected to interfere with the study drug).
5. Clinically significant abnormal values for hematology, serum chemistry, or urinalysis at Screening as deemed appropriate by the Investigator, including:
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than 1.5 × the upper limit of normal (ULN)
b. Total bilirubin greater than 1.5 × ULN unless due to Gilbert’s syndrome or if considered to be normal variability in the absence of other clinically relevant liver impairment, as approved by Medical Monitor
6. Clinically significant abnormal physical examination, vital signs, or 12-lead ECG at Screening as deemed appropriate by the Investigator.
7. History of respiratory disease including, but not limited to asthma and COPD and must not be under active treatment for an underlying respiratory disease. No family history of bronchial asthma. Not having severe allergic rhinitis.
8. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.

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)
Allocation is not concealed. The participant will be sequentially assigned to cohorts.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The site will allocate a sequential participant number on enrollment
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
11/10/2021
Actual
24/10/2021
Date of last participant enrolment
Anticipated
26/11/2021
Actual
6/01/2022
Date of last data collection
Anticipated
3/01/2022
Actual
28/01/2022
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19984 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 34692 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 309160 0
Commercial sector/Industry
Name [1] 309160 0
Receptor Life Sciences Australia Pty Ltd
Country [1] 309160 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Receptor Life Sciences Australia Pty Ltd
Address
58 Gipps Street, Collingwood, VIC 3066, Australia
Country
Australia
Secondary sponsor category [1] 310607 0
None
Name [1] 310607 0
Address [1] 310607 0
Country [1] 310607 0
Other collaborator category [1] 281920 0
Commercial sector/Industry
Name [1] 281920 0
Novotech (Australia) Pty Limited
Address [1] 281920 0
Level 3, 235 Pyrmont Street
Sydney, NSW 2009, Australia
Country [1] 281920 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309023 0
Bellberry Limited
Ethics committee address [1] 309023 0
Ethics committee country [1] 309023 0
Australia
Date submitted for ethics approval [1] 309023 0
13/08/2021
Approval date [1] 309023 0
03/09/2021
Ethics approval number [1] 309023 0
2021-02-801

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112682 0
Dr Kristi McLendon
Address 112682 0
Q-Pharm Pty Ltd,
Level 5 Clive Berghofer Cancer Centre Research Centre, 300c Herston Road, Herston, QLD 4006
Country 112682 0
Australia
Phone 112682 0
+61 7 38453620
Fax 112682 0
Email 112682 0
[email protected]
Contact person for public queries
Name 112683 0
Andrea Leone-Bay
Address 112683 0
Receptor Life Sciences
1200 Fifth Avenue, Suite 1400 Seattle, WA 98101
Country 112683 0
United States of America
Phone 112683 0
+1203 241 5716
Fax 112683 0
Email 112683 0
[email protected]
Contact person for scientific queries
Name 112684 0
Kelly Kraft
Address 112684 0
Receptor Life Sciences
1200 Fifth Avenue, Suite 1400 Seattle, WA 98101
Country 112684 0
United States of America
Phone 112684 0
+1845 797 8355
Fax 112684 0
Email 112684 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


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.