A Phase 2A Study to Investigate the Safety and Preliminary Analgesic Efficacy of Oral Trichomylin® in Male and Female Participants 18 Years of Age and Above With Advanced Cancer and Moderate to Severe Cancer-Related Pain
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 3
- 主要终点
- Number of Participants That Reach the Stable Dose during Dose Titration and Respond to Average Pain from Baseline to Investigational Product Discontinuation
研究概览
简要总结
This will be a proof-of-concept, single arm study with a maximum of 20 patients to evaluate preliminary analgesic efficacy and safety of Trichomylin® in patients with advanced cancer (male and female) who suffer from moderate to severe chronic pain and who are taking a stable dose of long-acting opioid therapy for at least 1 week prior to screening.
详细描述
This study will consist of a screening visit, treatment, and safety follow-up period. There will be an initial patient determined titration phase, using escalated doses of Investigational Product, to reach a dose that achieves symptom relief with tolerable side effects. Each capsule of Trichomylin® contains a fixed ratio of 5 mg delta-9-tetrahydrocannabinol: 5 mg cannabidiol: 5 mg cannabichromene. Participants can titrate up to a maximum of 2 capsules twice daily (total of 4 capsules). This will be followed by a 5 day assessment period of the stable dose determined in collaboration with clinicians.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has voluntarily agreed to study participation by giving written informed consent and must be ≥18 years of age on the day of signing the informed consent form (ICF).
- •Participant has advanced solid malignant tumors not amenable to curative-intent therapy (locally advanced unresectable or metastatic).
- •Participant life expectancy is ≥3 months at screening according to investigator's best judgement.
- •Participant has a clinical diagnosis of moderate to severe cancer-related pain with average daily pain score to be ≥4 for at least 4 out of the 7-day screening period, despite ongoing opioid treatment, as evidenced by their response to the BPI-SF Question #5 on the Numeric Rating Scale (NRS).
- •Participant is taking a stable dose of opioid therapy (Step III according to the World Health Organization [WHO] analgesic ladder) for at least 1 week prior to screening to relieve cancer-related pain.
- •Participant has adequate organ function, as indicated by the following laboratory values, at screening:
- •Baseline serum electrolytes must be within the normal range per local laboratories (for baseline serum electrolytes that are out of range, these may be corrected, and the potential participant may be rescreened).
- •Stable renal function (estimated glomerular filtration rate [eGFR] >15).
- •Total bilirubin (TBIL) ≤1.5 x upper limit of normal (ULN); or ≤3 x ULN for participants with Gilbert's syndrome.
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN or ≤5 x ULN for participants with liver metastases.
- •Participant has stable cardiac function, as determined by:
- •No clinically significant ECG waveform abnormalities.
- •QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤470 msec, as determined by the mean QTcF values from the ECG assessments at screening (one triplicate).
- •Participant can tolerate oral medications including capsules.
- •Participant is willing to take a medication which may exhibit psychoactive effects.
- •Participant must discontinue the use of the following medications 7 days before the start of study intervention and for the duration of the trial, unless in the opinion of the investigator and sponsor, the medication will not interfere with the study: herbal supplements or related products which are cytochrome P450 (CYP) 2E1, CYP3A4, or P-glycoprotein substrates, or which are strong inhibitors of the CYP3A4 and/or CYP3A5 pathways or which are known CYP3A4 inducers (this includes grapefruit and Seville oranges juice or related products, and St. John's wort).
- •Participant must not engage in medicinal or recreational use of any cannabinoid containing substance, in any form, within 30 days prior to screening and be willing to abstain from medicinal or recreational use of cannabis and other cannabinoid compounds (other than the Investigational Product) for the duration of the study.
- •Participant must have a negative urine drug screen for cannabinoids at screening and prior to dosing at Day 1; one repeat test may be conducted for a suspected false positive result.
- •Participant must not have any current or past allergic or adverse reaction or known sensitivity to olive oil, gelatine, glycerin, and titanium dioxide, or to cannabinoid-like substances (including but not limited to dronabinol, marinol, nabilone, marijuana, cannabis, THC, or cannabinoid oil).
- •Female participants are eligible to enter and participate in the study if they are of:
- •Non-childbearing potential.
- •Childbearing potential with a negative serum pregnancy test at screening (within 7 days of the first dose of Investigational Product) and agree to use contraception before study entry and throughout the study until 3 months after the last administered dose of the Investigational Product.
- •Male participants are eligible to enter and participate in the study if they are vasectomized or agree to the use of contraception during the study treatment period and for at least 3 months after the last administered dose of the Investigational Product.
- •Participants, in the opinion of the investigator, should understand the nature of the study, be able to participate in all planned assessments, complete all required tests, and be likely to comply with all study procedures.
排除标准
- •Female participants who are pregnant or lactating.
- •Participant has uncontrolled psychiatric disorders (severe depression or anxiety, personality disorder, psychosis, or schizophrenia).
- •Participant has a family history of schizophrenia.
- •Participant has current or history of suicidal behavior or ideation assessed by Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Participant has any known or suspected history of a diagnosed dependency disorder, including opioid abuse, current heavy alcohol consumption (i.e. more than 10 units of alcohol per week or 4 units on any given day [1 unit = 150 mL of wine, 260 mL of beer, or 45 mL of 40% alcohol]), current use of an illicit drug or current non-prescribed use of any prescription drug (Alcohol, Smoking and Substance Involvement Screening Test [ASSIST]).
- •Participant has engaged in medicinal or recreational use of any cannabinoid containing substance, in any form within the 30 days prior to screening.
- •Participant is within the first cycle of a new line of anticancer therapy (including but not limited to chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the start of the screening period.
- •Participant has had any major surgery within 4 weeks prior to screening.
- •Participant has an active infection requiring systemic treatment at the start of the study treatment.
- •Participant has cirrhosis or severe hepatic impairment defined as AST and ALT >3 x ULN or >5 x ULN for participants with liver metastases.
- •Participant has any of the following cardiovascular criteria:
- •a. Current evidence of unstable angina or another form of symptomatic cardiac ischemia b. Acute myocardial infarction ≤3 months prior to screening c. Heart failure of New York Heart Association Classification III or IV ≤3 months prior to screening d. Grade ≥2 ventricular arrhythmia ≤3 months prior to screening e. Cerebrovascular Accident (CVA) or Grade ≥2 Transient Ischemic Attack (TIA) ≤6 months prior to screening f. Grade ≥2 hypertension that cannot be managed by standard anti-hypertension medications before initiation of treatment g. Syncope or seizure ≤3 months before screening.
- •Participant has a history or presence of gastrointestinal disease or other condition known to interfere with the absorption of drugs.
- •Participant has intractable vomiting.
- •Participant has any other condition or abnormality that, in the investigator's judgement after medical interview, physical examination, and/or screening and baseline investigations, renders participant unfit for the study or precludes the participant's safe participation in and completion of the study.
- •Participant has concurrent participation in another therapeutic clinical trial or participation in another clinical trial within 30 days prior to the enrolment in this trial.
研究组 & 干预措施
Trichomylin®
Trichomylin® capsule (5 mg delta-9-tetrahydrocannabinol: 5 mg cannabidiol: 5 mg cannabichromene)
干预措施: Trichomylin® capsule (5 mg delta-9-tetrahydrocannabinol: 5 mg cannabidiol: 5 mg cannabichromene) (Drug)
结局指标
主要结局
Number of Participants That Reach the Stable Dose during Dose Titration and Respond to Average Pain from Baseline to Investigational Product Discontinuation
时间窗: Baseline and Investigational Product Discontinuation, up to 23 days
Participants have reached their "stable dose" and respond to average pain as entered in response to the BPI-SF Question #5, where response is defined as having a baseline of ≥30% from baseline at the Investigational Product discontinuation visit.
Change in Average Pain from Baseline to End of the Titration
时间窗: Baseline and End of Dose Titration, up to 14 days
Average pain as entered in response to the BPI-SF Question #5.
Change in Average Pain Scores from Baseline to Investigational Product Discontinuation
时间窗: Baseline and Investigational Product Discontinuation, up to 23 days
The Brief Pain Inventory Short Form (BPI-SF) is a standardized scale used for capturing participant reported symptom assessments related to pain severity and the resulting functional interference caused by pain. The BPI-SF has a numerical rating scale used by participants to indicate their level of pain. Participants are asked to assign a number that best describes their pain on average from 0 = no pain, to 10 = pain as bad as you can imagine, at the same time every day during the Screening period (Day -7 to Day -1) and enter this number in response to the BPI-SF Question #5 on the evaluation form.
Proportion of Responders to Average Pain from Baseline to Investigational Product Discontinuation
时间窗: Baseline and Investigational Product Discontinuation, up to 23 days
Average pain as entered in response to the BPI-SF Question #5, where response is defined as having a baseline of ≥30% from baseline at the Investigational Product discontinuation visit.
Number of Participants That Reach the Stable Dose during Dose Titration
时间窗: Baseline (i.e. Day 1 Dose Titration) and Stable Dose Day 1, up to 14 days
Investigational Product will be titrated up incrementally until participants achieve their "optimal dose" that achieves symptom relief with tolerable side effects or to a maximum of 2 capsules twice daily. Once participants have had 2 full days (at minimum) of treatment at this dosage, this will then be considered their "stable dose".
Change in Pain Interference from Baseline to End of the Titration
时间窗: Baseline and End of DoseTitration, up to 14 days
Pain interference is scored as the mean of the seven interference items and entered in response to the BPI-SF Question #9.
Change in Pain Interference from Baseline to Investigational Product Discontinuation
时间窗: Baseline and Investigational Product Discontinuation, up to 23 days
Pain interference as entered in response to the BPI-SF Question #9.
次要结局
- Incidence of Adverse Events of Special Interest(Baseline and End of Safety Follow-Up, up to 56 days)
- Proportion of responders in Brief Pain Inventory Short Form from Baseline to Investigational Product Discontinuation(Baseline and Investigational Product Discontinuation, up to 23 days)
- Change in Depression, Anxiety and Stress Scale - 21 Items from Baseline to Investigational Product Discontinuation(Baseline and Investigational Product Discontinuation, up to 23 days)
- Change in Subjective Measures of Symptom Change from Baseline to Investigational Product Discontinuation(Baseline and Investigational Product Discontinuation, up to 23 days)
- Incidence of Treatment Emergent Adverse Events(Baseline and End of Safety Follow-Up, up to 56 days)
- Change in Brief Pain Inventory Short Form from Baseline to Investigational Product Discontinuation(Baseline and Investigational Product Discontinuation, up to 23 days)
- Incidence of Serious Adverse Events(Baseline and End of Safety Follow-Up, up to 56 days)
- Change in Electrocardiogram From Baseline to Investigational Product Discontinuation(Baseline and Investigational Product Discontinuation, up to 23 days)
- Incidence of Adverse Events leading to Discontinuation of Study Treatment(Baseline and End of Safety Follow-Up, up to 56 days)
- Change in Quality of Life and Functional Status from Baseline to Investigational Product Discontinuation(Baseline and Investigational Product Discontinuation, up to 23 days)
- Use of Oral Morphine Equivalents from Baseline to Investigational Product Discontinuation(Baseline and Investigational Product Discontinuation, up to 23 days)