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Trial registered on ANZCTR


Registration number
ACTRN12617000642381
Ethics application status
Approved
Date submitted
28/04/2017
Date registered
3/05/2017
Date last updated
13/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A safety study of BTX1503 Solution in Healthy Volunteers
Scientific title
An Open-Label Study to Evaluate the Safety and Tolerability of BTX1503 Solution in Healthy Volunteers
Secondary ID [1] 291800 0
BTX.2017.001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acne 303031 0
Condition category
Condition code
Skin 302489 302489 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BTX1503 5% Solution, applied topically to the face using a supplied swab.
Participants will receive a 1mL dose either once (QD) or twice daily (BD) on Day 1.
Following a washout period, participants will receive a further 14 days of treatment starting on Day 8. Doses will be escalated for each subsequent cohort enrolled with the following doses:
Cohort 1: 1 mL of BTX1503 5% Solution QD
Cohort 2: 1 mL of BTX1503 5% Solution BID (12 hours apart)
Cohort 3: 3 mL of BTX1503 5% Solution QD
Cohort 4: 3 mL of BTX1503 5% Solution BID (12 hours apart)

For participants receiving QD dosing, dosing will occur each day at the clinical site at
the same time (+/-1 hour) in the morning (applied by clinical site staff). Participants receiving BID dosing will be instructed in how to apply study drug when not at the clinical site. For participants receiving BID dosing, the first application of study drug will occur at the study site on Day 8 in the morning and the second application will be self-administered by the participant 12
hours (+/-1 hour) later. Participants will come to the study site for their morning application of study drug and their evening application will be self-administered.

For participants doing a self-administered application of study drug, a diary will be maintained documenting compliance with application of the self-administered application. Each dose of study drug will be applied to the entire face. Participants will be asked to apply the total amount of study drug per application evenly, as best as possible, to cover all the face. In addition, participants will be required to return all used and unused study drug at each visit where the study site will assess compliance.
Intervention code [1] 297914 0
Treatment: Drugs
Comparator / control treatment
Comparing between the four cohorts:
Cohort 1: 1 mL of BTX1503 5% Solution QD
Cohort 2: 1 mL of BTX1503 5% Solution BID (12 hours apart)
Cohort 3: 3 mL of BTX1503 5% Solution QD
Cohort 4: 3 mL of BTX1503 5% Solution BID (12 hours apart)
Control group
Dose comparison

Outcomes
Primary outcome [1] 301913 0
To evaluate the safety of BTX1503 administered as a single dose either once (QD) or twice (BID) on Day 1 followed by a washout period, then starting on Day 8, either once (QD) or twice daily (BID) for 14 days.

Assessed by: Safety will be assessed through collection of vital signs (temperature, blood pressure and pulse), adverse events, cutaneous tolerability assessments, and laboratory findings (blood counts, chemistry, and urinalysis). Urine drug tests will be conducted for drugs of abuse, including the presence of tetrahydrocannibidiol (THC).
Timepoint [1] 301913 0
Timepoint: Adverse events will be monitored from time of consent through the end of study (day 23). Vital signs will be taken prior to and 2, 4, 8, and 24 hours after the first study drug application on Day 1 and prior to study drug application on Days 8, 15, and 21. Blood samples for blood counts and chemistry and urine for urinalysis will be obtained prior to and 12 hours after the first dose application and prior to study drug application on Days 8, 15, and 21. Urine testing for drugs of abuse, including THC, will be conducted prior to and 12 and 24 hours after the morning application on Day 1 and Day 21. Cutaneous tolerability assessments will be done prior to study drug application on Day 1 and Days 8 through 21. On Days 1, 8, 15 and 21 cutaneous tolerability will also be assessed 1 hour after the morning study drug application. On Days 1 and 21, additional assessments will be done 12 and 24 hours after the morning application and 48 hours after the morning application on Day 21.
Secondary outcome [1] 334265 0
The pharmacokinetics (PK) of BTX1503 with QD or BID dosing will be established in healthy volunteers.
Assessed by: collecting blood samples for analysis. PK parameters include – Cmax, Tmax, AUC
Timepoint [1] 334265 0
Timepoint: Blood samples will be collected within 15 minutes prior to the initial study drug application and at 30, 60 and 90 minutes and 2, 2.5, 3, 4, 6, 8 and 12 hours, and 24 hours after the first single dose. For participants receiving BID dosing, samples will also be taken at 30, 60 and 90 minutes and 2, 2.5, 3, 4, 6, and 8 hours after the second application on Day 1.
During the multiple dose (14-day) period, trough levels will be obtained before the daily application on Day 15. On Day 21, blood samples will be taken for PK assessments at pre-application (15 minutes before dosing), 30, 60 and 90 minutes and 2, 2.5, 3, 4, 6, 8 and 12 hours, 24 hours and 48 hours after the first application. For participants receiving BID dosing, samples will also be taken at 30, 60 and 90 minutes and 2, 2.5, 3, 4, 6, and 8 hours after the second application on Day 21.

Eligibility
Key inclusion criteria
To be included in the study, healthy volunteers must meet the following inclusion criteria.
1. Participant (or legal guardian) has the ability and willingness to sign a written informed consent.
2. Participant is of either gender between 18 and 65 years of age, inclusive.
3. Participant is in good general health without clinically significant haematological, cardiac, respiratory, renal, endocrine, gastrointestinal, psychiatric, hepatic, or malignant disease, as determined by the investigator.
4. Participant has suitable venous access for blood sampling.
5. Participant is able and willing to complete the study and to comply with all study instructions and attend the necessary visits.
6. Participant must be willing to use the facial cleansers provided (Dove or Neutrogena soap) throughout the study.
7. Participant must be willing to refrain from using facial products other than the facial cleansers provided, shaving cream, and sunscreens. Shaving cream and cleansers cannot be used within 5 minutes prior to, or for 4 hours after application of study medication; sunscreens cannot be applied less than 4 hours prior to or after application of study medication.
8. Participant must be willing to refrain from use of facial make-up throughout the study except for eye make-up and lipstick.
9. Participant agrees to not use marijuana products throughout the study.
10. Male participants and their partners must agree and commit to use a barrier method of contraception.
11. A negative urine pregnancy test (UPT) result for all women.
12. Sexually active women must agree to use:
a. One of these highly effective contraception methods
i. Intrauterine device (IUD); hormonal (injections, implants, transdermal patch, vaginal ring; tubal ligation; partner vasectomy, OR
b. Oral contraceptives WITH a barrier method (listed below), OR
c. Two barrier forms of contraception (listed below)
i. Male or female condom; diaphragm; cervical cap; contraceptive sponge.
13. Males participants must refrain from sperm donation during the study treatment period until 90 days post study drug administration.
14. Male participants must agree to keep their face clean shaven throughout the study and use the same method for shaving as was used for the 4 weeks prior to the Screening Visit.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
If a healthy volunteer meets any of the following exclusion criteria, they may not participate in the study.
1. Female participants who are pregnant, trying to become pregnant, or breast feeding.
2. Participant with history of known or suspected intolerance to dimethicone containing products, or drug product excipients (hexamethyldisiloxane, polymethylsiloxane, and polypropylene glycol (PPG) 15 stearyl ether).
3. Participant has used any marijuana products, via any route, within 4 weeks prior to the Screening Visit. A urine drug test positive for THC will exclude the participant.
4. Participant has sunburns, unevenness in skin tones, tattoos, scars, excessive hair, freckles, birthmarks, moles, or other skin damage or abnormality which impacts the ability to evaluate the skin of the face.
5. Participant has clinically significant skin diseases that may contraindicate participation, including psoriasis, eczema, atopic dermatitis, moderate to severe acne, dysplastic nevi, or other skin pathologies, or a history of skin cancer.
6. Participant has had any major illness within 4 weeks of the Screening Visit.
7. Participant has any clinically significant abnormal laboratory assessment(s) (blood counts, chemistry, or urinalysis), that, in the opinion of the investigator, may affect the evaluation of the study product or place the participant at undue risk.
8. Participant has known HIV infection.
9. Participant has a clinically relevant history of or current evidence of abuse of alcohol or other drugs. If the urine drug screen at the Screening Visit is positive for any drugs of abuse, the participant is not eligible to participate.
10. Participant has a clinically relevant history or currently suffering from any disease or condition that, in the opinion of the investigator, may affect the evaluation of the study product or place the participant at undue risk. This may include respiratory (including chronic asthma requiring repetitive drug interventions), gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, or connective tissue diseases or disorders.
11. Participant has received any investigational product or has had any procedure to the face within 4 weeks of the Screening Visit or is scheduled to receive an investigational product (other than the study product) or procedure to the face during the study.
12. Participant has used systemic or other immunosuppressive medications within 4 weeks of the Screening Visit (inhaled corticosteroid less than or equal to 1000 microgram daily dose is acceptable).
13. Participant is currently using any medication that, in the opinion of the investigator, may affect the evaluation of the study product or place the participant at undue risk.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This is an open-label, non-randomised, single- and multiple-escalating dose, Phase 1a study. Healthy volunteers will receive a single dose (QD or BID) of the study drug (BTX1503) on Day 1 followed by a washout period. If the maximum tolerated dose (MTD) is not observed after the single dose, participants will begin a 14-day treatment period with BTX1503 and the second dose cohort will begin. A total of four escalating dose cohorts will be evaluated sequentially. Up to 24 healthy volunteers (minimum 20; 5 per cohort) will be enrolled.
Participants will be enrolled sequentially and will be aware of the cohort to which they are being enrolled. There will be no attempts in this study to blind the dosing that participants will receive.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 15856 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 296302 0
Commercial sector/Industry
Name [1] 296302 0
Botanix Pharmaceuticals Ltd
Address [1] 296302 0
68 Aberdeen Street
Northbridge, WA 6006, Australia
Country [1] 296302 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Botanix Pharmaceuticals Ltd
Address
68 Aberdeen Street
Northbridge, WA 6006, Australia
Country
Australia
Secondary sponsor category [1] 295229 0
None
Name [1] 295229 0
Address [1] 295229 0
Country [1] 295229 0
Other collaborator category [1] 279548 0
Commercial sector/Industry
Name [1] 279548 0
Novotech (Australia Pty Limited
Address [1] 279548 0
Level 3, 235 Pyrmont Street
Pyrmont NSW 2009
Country [1] 279548 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297532 0
QIMR Berghofer Medical Research Institute-HREC
Ethics committee address [1] 297532 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Ethics committee country [1] 297532 0
Australia
Date submitted for ethics approval [1] 297532 0
Approval date [1] 297532 0
29/03/2017
Ethics approval number [1] 297532 0

Summary
Brief summary
Purpose
The purpose of this study is to investigate how safe and tolerable single and repeat doses of BTX1503 solution are in healthy volunteers. The study will look at whether the body adsorbs cannabidiol (CBD). by analysing the levels of CBD in blood at various times after drug administration. The application site will also be monitored for reactions and irritation.
Study participants
Healthy adults, aged between 18 and 65 years, inclusive, will participate.
Experimental Treatment
The study will investigate single and multiple doses of BTX1503 solution applied to the face. The components of BTX1503 have all been used in products that are applied to the skin. There will be four (4) different treatment cohorts with up to six (6) participants in each cohort.
Cohort 1: 1 mL of BTX1503 5% Solution will be applied as a single dose in the first part of the study and then, after washout period, a single application will occur each day in the clinic for 14 days during the second part of the study.
Cohort 2: 1 mL of BTX1503 5% Solution will be applied twice on Day 1 (12 hours apart) in the first part of the study and then, after washout period, twice daily applications will occur (one in the clinic and one self-applied) for 14 days during the second part of the study.
Cohort 3: 3 mL of BTX1503 5% Solution will be applied as a single dose in the first part of the study and then after washout period, a single application will occur each day in the clinic for 14 days during the second part of the study.
Cohort 4: 3 mL of BTX1503 5% Solution will be applied twice on Day 1 (12 hours apart) in the first part of the study and then after washout period twice daily applications will occur (one in the clinic and one self-applied) for 14 days during the second part of the study.
The study consists of a Screening Visit (up to 14 days before receiving the study treatment), a confinement visit starting on the morning of Day 1 and lasting approximately 24 hours, daily applications at the clinic on Day 8 through Day 20, a second confinement on Day 21 lasting 24 hours and 1 follow up visit on Day 23.
The maximum study duration for any participant from screening visit to last clinic visit is 37 days.
Tests and procedures which are conducted at some, or all visits during the study include: a brief review of your body systems, vital signs measured, blood and urine sampling.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74354 0
Dr Paul Griffin
Address 74354 0
Q-Pharm Pty Limited, Level 5, 300C Herston Road, Herston QLD, 4006
Country 74354 0
Australia
Phone 74354 0
+61 7 3845 3636
Fax 74354 0
Email 74354 0
P.Griffin@qpharm.com.au
Contact person for public queries
Name 74355 0
Dr Michael Thurn
Address 74355 0
Botanix Pharmaceuticals Limited
68 Aberdeen Street, Northbridge WA 6003
Country 74355 0
Australia
Phone 74355 0
+61 2 6362 7663
Fax 74355 0
Email 74355 0
mthurn@botanixpharma.com
Contact person for scientific queries
Name 74356 0
Mr Mark Davis
Address 74356 0
Botanix Pharmaceuticals Limited
252 North Radnor Chester Road, St. Davids, PA 19087 USA
Country 74356 0
United States of America
Phone 74356 0
+1 925 3361055
Fax 74356 0
Email 74356 0
mdavis@botanixpharma.com

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary