Trichomylin® Safety, Tolerability & Pharmacokinetics in Healthy Adults and First in Human Osteoarthritis Pain Evaluation

NCT04867057 | Completed Phase 1 DMC

• 1 other identifier: Z-TRI-10001
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first in human, randomized, double-blind, placebo-controlled SAD (with food effect) followed by a MAD study of Trichomylin® conducted in healthy adult participants.

Conditions

Healthy; Osteoarthritis

Keywords

Cannabinoid; Safety and Tolerability; Pharmacokinetics; Pharmacodynamics; Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Percentage and severity of unexpected Serious Adverse Events (SAEs)

  To investigate the safety and tolerability of Trichomylin by assessment of the percentage and severity of SAEs following administration of oral soft-gel capsules in Single Ascending Dose (SAD Cohort) and Multiple Ascending Doses (MAD Cohort)

  Through study completion, an average of 1 year

Secondary Outcomes (4)

• Rate and extent of absorption of Trichomylin by assessment of the observed Maximum Plasma Concentration (Cmax)

  SAD cohort: Day 1 through Day 21; MAD cohort: Day 1 through 30

• Rate and extent of absorption of Trichomylin by assessment of the observed Time to Maximum Plasma Concentration (Tmax)

  SAD cohort: Day 1 through Day 21; MAD cohort: Day 1 through 30

• Rate and extent of elimination of Trichomylin by assessment of the observed Apparent Terminal Elimination Rate Constant (Kel)

  SAD cohort: Day 1 through Day 21; MAD cohort: Day 1 through 30

• Exposure of Trichomylin by assessment of area under the drug concentration-time curve (AUC).

  SAD cohort: Day 1 through Day 21; MAD cohort: Day 1 through 30

Study Arms (4)

Experimental: Trichomylin for SAD

EXPERIMENTAL

18 out of 24 subjects were randomized to receive Trichomylin in a single dose.

Drug: Trichomylin for SAD

Placebo Comparator: Placebo for SAD

PLACEBO COMPARATOR

6 out of 24 subjects were randomized to receive placebo in a single dose.

Drug: Placebo for SAD

Experimental: Trichomylin for MAD

EXPERIMENTAL

13 out of 17 subjects were randomized to receive Trichomylin in multiple doses.

Drug: Trichomylin for MAD

Placebo Comparator: Placebo for MAD

PLACEBO COMPARATOR

4 out of 17 subjects were randomized to receive Placebo in multiple doses.

Drug: Placebo for MAD

Interventions

Trichomylin for SAD DRUG

Healthy subjects meeting eligibility criteria were randomized to each dose cohort (up to four dose ascending cohorts) to receive either Trichomylin or Placebo. The study drug (Trichomylin or Placebo) will be administered orally as a single dose.

Experimental: Trichomylin for SAD

Placebo for SAD DRUG

Healthy subjects meeting eligibility criteria were randomized to each dose cohort (up to four dose ascending cohorts) to receive either Trichomylin or Placebo. The study drug (Trichomylin or Placebo) will be administered orally as a single dose.

Placebo Comparator: Placebo for SAD

Trichomylin for MAD DRUG

Healthy subjects meeting eligibility criteria were randomized to each dose cohort (up to three cohorts) to receive either Trichomylin or Placebo. The study drug (Trichomylin or Placebo) will be administered daily oral doses for a total of 9 days.

Experimental: Trichomylin for MAD

Placebo for MAD DRUG

Healthy subjects meeting eligibility criteria were randomized to each dose cohort (up to three cohorts) to receive either Trichomylin or Placebo. The study drug (Trichomylin or Placebo) will be administered daily oral doses for a total of 9 days.

Placebo Comparator: Placebo for MAD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female volunteers, aged 18 to 65 years (inclusive at the time of consent);
• Must have a Body Mass Index (BMI) ≥ 18 to ≤ 32 kg/m2 with weight ≥ 50 kg at Screening;
• Must have a negative urine drug screen at the Screening visit and the day before dosing (Day -1); one repeat urine drug may be conducted for a suspected false positive result;
• Must be willing to abstain from the use of cannabis and other cannabinoid compounds (other than the study drug) for the duration of the study (from the time of Screening until the EOS visit);
• Must be willing to abstain from smoking (including the use of tobacco or nicotine products and e-cigarettes) for the duration of the study (from the time of Screening until the EOS visit);
• Must not have any hepatic and/or renal impairment as judged by the PI;
• Must be willing and able to comply with all study procedures and be available for the duration of the study (from the time of Screening until the EOS visit);
• Must not be currently using anti-depressants (selective serotonin reuptake inhibitors \[SSRIs\], monoamine oxidase inhibitors \[MOAIs\], serotonin-norepinephrine reuptake inhibitors \[SNRIs\], or tricyclic anti-depressants \[TCAs\]) for 14 days or 5 half-lives of the drug, whichever is longer, prior to IP administration, and for the duration of the study;
• Must not have any current or past allergic or adverse reaction or known sensitivity to olive oil, gelatin, glycerin and titanium dioxide, or to cannabinoid-like substances (including but not limited to Dronabinol/Marinol/Nabilone/marijuana/cannabis/tetrahydrocannabinol \[THC\], cannabinoid oil);
• Females must be non-pregnant and non-lactating and must use two forms ("double contraception") of acceptable, highly effective contraception from Screening and for 12 weeks following the last dose of study drug. Double contraception is defined as a condom AND one other form of the following:
• Established hormonal contraception (with an approved oral contraceptive pill \[OCP\]);
• Depot or injectable birth control;
• A vaginal ring or an intrauterine device (\[IUD\], with or without hormones); OR
• Documented evidence of surgical sterilization as a single form of birth control, at least 6 months prior to Screening (e.g., tubal ligation, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy for women, OR vasectomy for men \[with documented azoospermia 90 days after procedure\] provided that partner is the sole sexual partner).
• Women not of childbearing potential must be post-menopausal (defined as cessation or regular menstrual periods for at least 12 months). Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) consistent with post-menopausal state based on lab reference ranges.

You may not qualify if:

• Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study and for 12 weeks after final study drug administration;
• Has a past or present clinically significant condition, which would prevent or limit study assessments in accordance with the protocol, with particular reference to renal and/or hepatic impairment, OR it would be in the best interests of the participant to not participate;
• Has been diagnosed with the following within 10 years of Screening: psychosis (secondary to, for example, substance abuse, major depression, a mood disorder with postpartum onset, bipolar disorder, schizophrenia, or borderline personality disorder), somatoform disorder(s) or chronic fatigue syndrome;
• Has a current/active diagnosis of generalized anxiety disorder, panic disorder, obsessive compulsive disorder, post- traumatic stress disorder, a simple phobia(s), anorexia nervosa or bulimia nervosa;
• Cognitive impairment and/or a psychiatric illness (e.g., dementia, Alzheimer's disease or psychosis), which in the opinion of the Investigator will prevent participants from reliably providing primary outcome data;
• Has significant suicidal ideation as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9);
• Regular use of alcohol within one month prior to the Screening visit (i.e. more than 10 units of alcohol per week or 4 units on any given day \[1 unit = 150mL of wine, 260 mL of beer, or 45mL of 40% alcohol\]);
• Symptomatic heart failure (per New York Heart Association \[NYHA\] guidelines), unstable angina, myocardial infarction, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to Screening;
• Has an abnormal ECG of clinical relevance at Screening or Baseline, including but not limited to the following:
• QTcF interval \> 450 msec
• Evidence of 2nd and 3rd degree atrioventricular (AV) block, or 1st degree AV block with PR interval \> 200ms, left bundle branch block (LBBB) or right bundle branch block (RBBB) at Screening or Baseline. Incomplete RBBB will not permitted.
• Has a history of risk factors including hypokalemia, family history of Long QT Syndrome, or prior use of medications that prolong the QT/QTc interval
• Has a resting heart rate \< 45 beats/minute, \> 100 beats/min upon one repeated measurement within 5 minutes;
• Has abnormal blood pressure outside specified limits (90 mm Hg \> Systolic \> 140 mm Hg and/or 50 mm Hg \> Diastolic \> 90 mm Hg) upon repeated measurement;
• Has clinically significant abnormalities in any of the clinical laboratory evaluations at Screening or Day -1 as determined by the Investigator;

Sponsors & Collaborators

• ZYUS Life Sciences Inc.: lead
• Novotech (Australia) Pty Limited: collaborator
• ZYUS Life Sciences Australia Pty Ltd: collaborator

Study Sites (1)

CMAX Clinical Research

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Osteoarthritis; Chronic Pain

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Study Officials

• Paul Wabnitz, Dr

  CMAX clinical research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: April 30, 2021
• Study Start: April 19, 2021
• Primary Completion: February 18, 2022
• Study Completion: May 30, 2022
• Last Updated: June 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)