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Trial registered on ANZCTR


Registration number
ACTRN12622000120774
Ethics application status
Approved
Date submitted
11/01/2022
Date registered
25/01/2022
Date last updated
25/01/2022
Date data sharing statement initially provided
25/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Is ZTL-106 effective in treating patients with chronic pain that resulted from a musculoskeletal injury?
Scientific title
A phase 2a, randomised, double-blind, placebo controlled study to evaluate the efficacy of ZTL-106 in treating patients with chronic pain as a result of a musculoskeletal injury
Secondary ID [1] 306142 0
None
Universal Trial Number (UTN)
U1111-1273-0863
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic non-cancer pain 324841 0
musculoskeletal injury 324973 0
Condition category
Condition code
Musculoskeletal 322281 322281 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is a double-blind, placebo controlled interventional trial.
Participants eligible to participate will be randomised to receive either ZTL-106 or Placebo. The investigational treatments will be administered as an oral oil twice daily, once in the morning and once in the evening for each participant for up to 6 weeks.
ZTL-106 is a 1:1 formulation of THC (10 mg/ml) : CBD (10 mg/ml) dissolved in medium-chain triglyceride (MCT) oil with a proprietary blend of terpenes (<0.1% v/v) and a natural lemon flavouring added.
Placebo will contain the MCT oil, terpenes and natural lemon flavouring. It does not contain any cannabinoids.
Administration will begin with an initial 2 week period of up titration, starting at 0.25ml (5mg total cannabinoids) for two days and then increasing the dose in 0.25ml (5mg total cannabinoids) increments every second or third day. Titration will target a maximal daily intake of 2 mls (40mg total cannabinoids) or until a maximum tolerable dose has been disinterred. Participant will maintain their maximal dose for the remaining 4 weeks up until week 6.
Participants adherence to the dosing regime will be assessed based on both a self-completed dosing diary and by weight the returned drug bottles.
Intervention code [1] 322553 0
Treatment: Drugs
Comparator / control treatment
Placebo will contain the MCT oil, terpenes and natural lemon flavouring. It does not contain any cannabinoids.
Control group
Placebo

Outcomes
Primary outcome [1] 330041 0
To evaluate the safety and tolerability of daily administration of ZTL-106 medicinal cannabis product in patients with chronic pain after musculoskeletal injury.
Timepoint [1] 330041 0
Incidence and severity of adverse events, clinical laboratory tests as compared to baseline and/or the 4 week run in period and after the 6 weeks treatment window.
Primary outcome [2] 330042 0
To evaluate the effect of daily administration of ZTL-106 medicinal cannabis product on pain interference with daily functions in patients with chronic pain after musculoskeletal injury.
Timepoint [2] 330042 0
Change in Brief Pain Inventory interference scale (BPI-I) scoring at week 4 and after 6 weeks as compared to baseline and/or the 4 week run in period
Secondary outcome [1] 404700 0
To evaluate the effect of daily administration of ZTL-106 medicinal cannabis product on severity of pain in patients with chronic pain after musculoskeletal injury.
Timepoint [1] 404700 0
Change in Brief Pain Inventory severity scale (BPI-S) scoring at week 4 and after 6 weeks as compared to baseline and/or the 4 week run in period .
Secondary outcome [2] 404701 0
To evaluate the effect of daily administration of ZTL-106 medicinal cannabis product on the joint-related (hip or knee) quality of life in patients with chronic pain after musculoskeletal injury
Timepoint [2] 404701 0
Depending on the participants previous injury, the change in Knee injury and Osteoarthritis Outcome Score (KOOS) – Quality of Life (QoL) subscale for knees or Hip disability and Osteoarthritis Outcome Score (HOOS) - QoL subscale for hips at week 4 and 6 as compared to baseline and/or the 4 week run in period.
Secondary outcome [3] 404702 0
To evaluate the effect of daily administration of ZTL-106 medicinal cannabis product on impression of improvement and satisfaction with the treatment in patients with chronic pain after musculoskeletal injury.
Timepoint [3] 404702 0
Change in Global Impression of Change reported by the patient (PGIC) at week 4 and 6 as compared to baseline and/or the 4 week run in period.
Secondary outcome [4] 404703 0
To evaluate the effect of daily administrations of ZTL-106 medicinal cannabis product on emotional function in patients with chronic pain after musculoskeletal injury.
Timepoint [4] 404703 0
Change in Hospital Anxiety and Depression Scale (HADS) at week 4 and 6 as compared to baseline and/or the 4 week run in period.
Secondary outcome [5] 404704 0
To evaluate the effect of daily administrations of ZTL-106 medicinal cannabis product on the frequency of significant pain events in patients with chronic pain after musculoskeletal injury.
Timepoint [5] 404704 0
Number of single individual pain events/flare ups considered =4 on a Numerical Rating Scale (NRS) in a 4 week period post treatment as compared to run in period.
Secondary outcome [6] 404705 0
To evaluate the effect of daily administrations of ZTL-106 medicinal cannabis product on physical functioning in patients with chronic pain after musculoskeletal injury.
Timepoint [6] 404705 0
Number of one leg rise (maximum sit to stands on one leg from a standardized height chair) at week 6 as compared to baseline.

Eligibility
Key inclusion criteria
• Adult male and female age 25-75 years, inclusive.
• Confirmed incidence of average pain severity of equal to or greater than 4 on a numeric rating scale.
• Chronic pain for more than 6 months prior to screening that followed a knee or hip musculoskeletal injury.
• Participant agrees to abide by all study restrictions and comply with all study procedures.
• Participants must be informed of the investigational nature of this study and give written informed consent and agree to provide a contact phone number.
• Male participants must agree to an approved contraception method. This criterion must be followed from the time of the first dose of study medication until the last follow-up visit.
• Females of childbearing potential must have a negative pregnancy test at the Screening Visit and at the baseline visit prior to randomisation.
• Must not have used recreational medicinal cannabis for the last 30 days and agree to cease recreational medicinal cannabis during the study treatment and follow up period.
Minimum age
25 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Changes to current medications, or commencement of any new medications including prescription drugs (except hormonal contraception), vitamins, or herbal supplements within 28 days prior to the Screening Visit and during the study treatment phase. Daily administration of 100 mg aspirin will be allowed as long as the dose is stable for 30 days prior to Screening.
• Known history of cardiovascular disorders such as bradycardia, (<50 beats/min.) or tachycardia (>100 beats/min.), cardiac arrhythmia or a history of arrhythmias, myocardial infarction, stroke or signs or symptoms of unstable coronary artery disease within the last year.
• Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg).
• Any medical condition that could account for the chronic pain (e.g., fibromyalgia) other than as a result of a previous musculoskeletal injury in the opinion of the clinical investigator.
• Recognised inflammatory condition (including rheumatoid arthritis, seronegative arthritis) that may influence the chronic pain in the opinion of the clinical investigator.
• Blood glucose, FBC, haemoglobin, platelets, creatinine, bilirubin, and AST/ALT outside the normal limits.
• Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the clinical investigator would pose a safety risk or interfere with appropriate interpretation of study data.
• History of major psychiatric illness.
• History of drug or alcohol abuse within 1 year prior to screening as per investigator judgement or a positive alcohol or urine drug screen.
• Clinically significant infection (including bacterial, fungal or mycobacterial) within four weeks prior to screening.
• History of disorder that may necessitate the use of antibiotics during the study period.
• Positive serology for HIV, HBV or HCV.
• Receipt of any live attenuated vaccines within 4 weeks prior to entry.
• Any medical condition that in the judgement of the investigator will exclude the patient from participating in the study.
• Surgery within 3 months prior to screening.
• Known allergy to cannabinoids or related compounds.
• Planned participation in an investigational drug or device study; or has received an investigational biopharmaceutical product within 6 months prior to screening, or an investigational non-biopharmaceutical product or device within 30 days prior to screening.
• Required to operate heavy machinery for the duration of the study.
• Unable to refrain from driving for the duration of the study.
• Have a current compensable injury claim.
• If, in the opinion of the clinical investigator, the participant appears unable to perform the needed responsibilities of the clinical study.
• Females who are pregnant, breast feeding or planning a pregnancy; females of childbearing potential and male participants with a partner of childbearing potential, who are unwilling or unable to use an acceptable method of contraception as outlined in this protocol from at least 21 days prior to the first dose of study medication and for 28 days after the last dose of study medication.
o Standard acceptable methods include abstinence or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, vasectomy, intrauterine device.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Safety will be assessed by summarising adverse events and clinical laboratory tests. Adverse events will be listed and summarised by system organ class and preferred terms (current version of MedDRA) per treatment group. Vital signs and clinical laboratory tests will be tabulated and summarised per treatment group. Adverse event severity will be graded according to the Common Terminolgoy Criteria for Adverse Events (CTCAE) grading criteria. The descriptive statistics will be presented in tables and by figures. All evaluable participants will be included in the analysis. Parameters will be assessed by dose cohort. Dose dependent parameters will be evaluated across dose cohorts to describe the dose-response profile.
The full analysis set will be used as the primary population to report efficacy data and to summarise baseline characteristics. This comprises all patients randomised into the study and will be analysed according to randomised treatment (intention-to-treat [ITT] principle), who received at least one dose of ZTL-106. Any important deviations from randomised treatment will be listed and considered when interpreting the efficacy data, sensitivity analysis on a modified ITT population may be conducted. ANCOVA (Analysis of covariance) models will be adopted using treatment as a fixed effect, and baseline BPI-I as a covariate. For the PROMs assessments (BPI, KOOS-QoL or HOOS-QoL, PGIC, NRS, HADS), the baseline will comprise of the average of all evaluable values from the 4 week run-in period and the Day 1 pre-dose value. For all other endpoints, baseline will be defined as the last evaluable value recorded prior to first dose of study medication.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/05/2022
Actual
Date of last participant enrolment
Anticipated
5/12/2022
Actual
Date of last data collection
Anticipated
31/03/2023
Actual
Sample size
Target
114
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 310486 0
Commercial sector/Industry
Name [1] 310486 0
Levin Health Ltd
Country [1] 310486 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Levin Health Ltd
Address
Carlow House
Suite 2-3, Level 6
289 Flinders Lane
Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 311651 0
None
Name [1] 311651 0
Address [1] 311651 0
Country [1] 311651 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310116 0
Bellberry
Ethics committee address [1] 310116 0
Ethics committee country [1] 310116 0
Australia
Date submitted for ethics approval [1] 310116 0
Approval date [1] 310116 0
23/11/2021
Ethics approval number [1] 310116 0

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

Contacts
Principal investigator
Name 116530 0
Prof Peter Brukner
Address 116530 0
La Trobe Sport and Exercise Medicine Research Centre
La Trobe University
Cnr Plenty rd and Kingsburry Drive
Bundoora, Vic 3086
Country 116530 0
Australia
Phone 116530 0
+610394792169
Fax 116530 0
Email 116530 0
p.brukner@latrobe.edu.au
Contact person for public queries
Name 116531 0
Matthew King
Address 116531 0
La Trobe Sport and Exercise Medicine Research Centre
La Trobe University
Cnr Plenty rd and Kingsburry Drive
Bundoora, Vic 3086
Country 116531 0
Australia
Phone 116531 0
+610394793531
Fax 116531 0
Email 116531 0
m.king@latrobe.edu.au
Contact person for scientific queries
Name 116532 0
Joanne Kemp
Address 116532 0
La Trobe Sport and Exercise Medicine Research Centre
La Trobe University
Cnr Plenty rd and Kingsburry Drive
Bundoora, Vic 3086
Country 116532 0
Australia
Phone 116532 0
+610394791428
Fax 116532 0
Email 116532 0
j.kemp@latrobe.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data will not be available, only aggregate data will be available through peer-reviewed publications.


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.