A Randomised, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Evaluate the Efficacy, Safety and Tolerability of 150 mg Sublingual Cannabidiol in Adults with Mild-to-Moderate Pain.
Promethean Health Pty Ltd
172 participants
Jul 5, 2023
Interventional
Conditions
Summary
Pain is extremely prevalent and highly impactful on quality of life. Both acute and chronic pain are routinely treated with paracetamol, non-steroidal anti-inflammatory drugs, monoamine reuptake inhibitors, anticonvulsant agents, and opioids. However, these treatments may have only modest efficacy in the treatment of pain and/or can have significant adverse effects that also interfere with quality of life (e.g., cognitive clouding, sedation, fatigue, weight gain). The high prevalence and high burden of disease associated with pain, combined with ineffectual treatments or treatments with significant adverse effects defines a clear unmet need for new well tolerated and effective therapeutic treatments that are not prone to abuse/misuse. This extends to the management of mild-to-moderate non-palliative pain. Cannabidiol (CBD) represents one such treatment for control of mild-to-moderate non-palliative pain. Three clinical trials and two observational studies demonstrated clear positive effects of chronic CBD dosing regimens on the management of a range of pain indications. This is a first-in-human (FIH) study for the Promethean Health CBD tablet. However, CBD been extensively investigated in human clinical trials at doses ranging from < 10 mg/day to up to 6,000 mg/day. The planned Promethean Health Pty Ltd clinical trial will investigate a total CBD daily dose of 150 mg/day for a period of 30 days. The dose level was selected within the TGA guidance for Schedule 3 registration (16). The 3 times a day dosing schedule was selected based on the half-life of the formulation (approximately 6 hours), with 3 times daily allowing the broadest dosing schedule that can be achieved through waking hours.
Eligibility
Inclusion Criteria21
- Must have given informed consent, before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
- Male or female 18 to 75 years of age
- Body mass index (BMI) less than or equal to 35.0 kg/m2. Exceptions may be permitted at the discretion of the Investigator for healthy participants with a BMI > 35 mg/m2.
- Presence of mild-to-moderate acute, subacute or chronic non-palliative pain for greater than or equal to 2 weeks (BPI-SF5 average pain score of 3-6) at the time of screening, and on Day 1, prior to dose administration. Pain may include, but is not limited to, pain due to injury, musculoskeletal pain, bone or joint-related pain, tendon or ligament-related pain, arthritis, fibromyalgia, bursitis, endometriosis etc .
- Participant currently requires stable use (stable usage for at least 14 days, in the opinion of the Investigator) of non-opioid simple analgesia to manage pain symptoms at screening and on Day 1, prior to dose administration. Note: simple analgesia may refer to the use of non-opioid pain medications or non-pharmacological therapies (examples may include, but are not limited to, hydrotherapy, use of transcutaneous electrical nerve stimulation, walking and/or exercise).
- With the exception of findings associated with the primary presentation of pain, participant is otherwise medically healthy, as determined by pre-study medical history and without clinically significant abnormalities at screening or on Day 1, prior to dose administration including:
- a. Physical examination without any additional clinically relevant findings
- b. Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after 5 minutes in supine or semi-supine position.
- c. Heart rate in the range of 45 to 100 beats/minute after 5 minutes rest in supine or semi-supine position.
- d. Body temperature (tympanic), between 35.5°C and 37.7°C.
- e. Electrocardiogram (ECG) without clinically significant abnormal findings.
- No clinically relevant findings in clinical laboratory blood and urinalysis tests as judged by the PI (or delegate), including evidence of adequate hepatic function, as defined by AST and ALT less than or equal to 2.5 X upper limit of normal.
- Female participants must be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or, if of child-bearing potential:
- a. Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on Day 1, prior to dose administration.
- b. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 31 days (30 days + a minimum of 5 x half-lives of Promethean Health CBD) after the last dose of study drug.
- c. If not exclusively in a same-sex relationship, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 31 days after the last dose of study drug.
- Male participants must:
- a. Agree not to donate sperm from the time of signing consent until at least 91 days (90 days + minimum of 5 x half-lives of Promethean Health CBD) after the last dose of study drug.
- b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception from the time of signing consent until at least 91days after the last dose of study drug.
- c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom from the time of signing consent until at least 91 days after the last dose of study drug.
- Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
Exclusion Criteria18
- Hypersensitivity or other clinically significant reaction to the study drug or its active ingredients.
- Participant is currently receiving treatment with an opioid analgesic, or any other Schedule 4, Schedule 8 or Schedule 9 analgesics listed in the most recent version of the Australian Therapeutic Goods Poisons Standard.
- Participant is receiving current treatment with a neuroleptic medication.
- Participant is receiving current treatment with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs).
- Participant has used cannabis (or its derivatives, synthetic or otherwise) within 28 days prior to first dose administration on Day 1.
- Major surgery (in the opinion of the PI [or delegate]) within 28 days of study drug administration on Day 1, or minor surgical procedures within 7 days of Day 1.
- In the opinion of the Investigator (or medically qualified designee), participant has any of the following:
- a. A history of significant cardiac disease
- b. Any current unstable serious illness or malignancy
- Positive alcohol breath test at Screening or on Day 1, prior to dose administration.
- Positive urine drugs of abuse test at Screening on Day 1, prior to dose administration.
- Participant is breastfeeding or pregnant or planning to breastfeed or become pregnant during the study.
- Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results.
- Active infection requiring systemic antibiotic, antifungal, or antiviral medication within 14 days prior to first dose of study drug.
- Active hepatitis B (Hep B), hepatitis C (Hep C), Epstein-Barr virus (EBV) or human immunodeficiency virus (HIV) infection.
- Received any vaccination within 14 days prior to first dose administration on Day 1 or plans to receive a vaccination during the study.
- Concurrent participation in another clinical trial, or participation in another clinical trial within 60 days prior to first dose administration on Day 1.
- Any other condition or prior therapy that in the opinion of the Investigator (or delegate) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
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Interventions
This is a randomised, double-blind, placebo-controlled Phase 3 registration parallel arm study to evaluate the efficacy, safety and tolerability of 150 mg Promethean Health Cannabidiol (CBD) 3 times daily, in adults experiencing mild-to-moderate pain. Promethean Health CBD Tablet is a plant-derived, highly purified CBD ((-) enantiomer (100%); minimum CBD content of greater than or equal to 98%), formulated as a nanoparticle encapsulation complexation tablet for sublingual delivery. Participants will take Promethean Health CBD tablet as oral sublingual tablets three times a day for 30 days (150 mg total daily dose), with each dose taken approximately 6 hours (± 2 hours) apart. Doses will divided as follows: • Dose 1: 2 x 30 mg tablets (60 mg total) • Dose 2: 2 x 30 mg tablets (60 mg total) • Dose 3: 1 x 30 mg tablet A total of up to 172 participants will be randomised to receive Promethean Health CBD or placebo, at a ratio of 1:1. 86 participants will receive Promethean Health CBD. During the treatment period, participants will be required to attend the clinic on days 1, 15 and 30 for study assessments. In addition participants will also be required to attend a telehealth appointment (or receive a phone call) on day 2, 8 and 22 to ascertain the use of concomitant medications and emergence of AEs, and to complete the BPI-SF, EQ-5D-5L and EQ-VAS questionnaires (Days 8 and 22 only). The end of study visit will be on Day 44. At the discretion of the site (in consultation with the participant) Days 8 and 22 may be conducted as a phone call/telehealth appointment or an in-person clinic visit. Clinical facility staff will administer the study drug only to participants included in this study following the procedures set out in this study protocol. Administration of study drugs will be recorded in the appropriate drug accountability records and the electronic case report form (eCRF). Participants will also maintain a diary to confirm the administration of the 3 doses of study drug each day. Each participant will only be given the study drug preparation carrying his/her study number.
Locations(6)
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ACTRN12623000404628