None listed
Conditions
Brief summary
Complex regional pain syndrome (CRPS) is a painful debilitating condition in a limb. This complex disorder is associated with abnormalities in skin, bone, and the autonomic, sensory and motor nerves which significantly impact the quality of life of patients suffering from this condition. Due to the complex and progressive nature of the disorder, the development of specific interventions for CRPS has been challenging. This is a double-blind, randomized, placebo controlled, single ascending dose study in healthy male and female subjects of a dronabinol containing pressurised metered dose inhaler (IRX211). The study will evaluate the safety and tolerability of escalating doses of IRX211 administered as a single inhaled dose in healthy volunteers (Primary Objective). It will also evaluate the systemic exposure of escalating doses of IRX211 administered as a single inhaled dose in healthy volunteers (Secondary Objective). The data collected from this study will be critical to inform the ongoing development of IRX211 as a treatment for CRPS.
Interventions
IRX211 is an inhaled formulation of dronabinol, administered through a pressurised metered dose inhaler, and is being developed for the treatment of patients with Complex Regional Pain Syndrome (CRPS). This Phase I study is a double-blind, randomized, placebo controlled, single ascending dose study in healthy male and female subjects.
The study will investigate the pharmacokinetics (PK), safety and tolerability of single escalating doses of IRX211. The study will enrol up to 4 cohorts of 8 parti
IRX211 is an inhaled formulation of dronabinol, administered through a pressurised metered dose inhaler, and is being developed for the treatment of patients with Complex Regional Pain Syndrome (CRPS). This Phase I study is a double-blind, randomized, placebo controlled, single ascending dose study in healthy male and female subjects. The study will investigate the pharmacokinetics (PK), safety and tolerability of single escalating doses of IRX211. The study will enrol up to 4 cohorts of 8 participants. For each dose cohort, participants will be randomized accordingly (3:1) to ensure 6 will receive IRX211 and 2 the placebo. The cohorts will enrol in sequential order depending on when participants join the study. They will enrol in either Cohort 1, 2, 3 or 4 to receive one of four doses of IRX211 or placebo respectively. Intended trial doses will include 0.5mg, 1mg, 2.5mg or 5mg. The first cohort will include the initial dosing of a sentinel group (1 IRX211 and 1 placebo participant). The remaining 6 participants in the cohort (5 IRX211 and 1 placebo) will be dosed if, in the opinion of the investigator or delegate, there are no significant safety concerns identified in the sentinel participants within the first 24 hours after administration of the dose (IRX211 or placebo). The study will dose ascend once safety data and PK data are reviewed by the Safety Review Committee (SRC). The SRC will also advise if sentinel dosing will be required for subsequent cohorts. Participants will be screened within 28 days prior to dosing. Participants will report to the study site on the day prior to administration of IRX211 to confirm eligibility. Participants will complete at least a 10 hour fast prior to study drug administration. Participants will receive either IRX211 or placebo on Day 1. Participants will be trained to self-administer a single dose of the study drug via the inhaler under close supervision. Participants will remain at the study site for observation through to 8 hours post-dose and will complete an end of study visit 7 ± 2 days after dosing.
Sponsors
InhaleRx Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Each participant must meet all the following criteria to be enrolled in this study: 1. Aged between 18 and 55 years (inclusive at Day 1). 2. Free from clinically significant (in the opinion of the Investigator) illness or disease as determined by their medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory determinations. 3. BMI between 18 and 32 kg/m2 (inclusive) at Screening. 4. Weight greater or equal to 50.0 kg at Screening. 5. Adequate venous access in both arms for collection of a number of blood samples. 6. Capable of understanding the purposes and risks of the study and able to provide written informed consent before any study-specific screening procedures are performed. 7. Willing and able to adhere to all protocol requirements, including willingness to comply with scheduled visits, and tolerance to dosing using an inhaler. 8. The subject is able to perform deep inhalations with FEV1 more than 80%. 9. Female subjects of childbearing potential must be abstinent from heterosexual intercourse or agree to use an acceptable form of contraception with a male sexual partner and agrees to refrain from egg donation. 10. Male subjects must be abstinent from heterosexual intercourse or agree to use an acceptable form of contraception with a female sexual partner of childbearing potential and agrees to refrain from sperm donation.
Exclusion criteria
Participants who meet any of the following criteria will be excluded from this study: 1. History of coronary disease, peripheral vascular disease, cerebrovascular accident, transient ischemic attack, uncontrolled hypertension or signs/symptoms of ischemic heart disease. 2. History of acute or severe bronchial asthma (excluding childhood or exercise induced asthma), diagnosed obstructive sleep apnea, hypoxia, hypoxemia, hypercarbia, or other obstructive airway disease or any condition that may increase the risk for respiratory depression. 3. History of neurologic conditions such as seizures (excluding single febrile seizures during childhood) or convulsive disorders (including epilepsy), severe head injury or increased intracranial pressure. 4. Any concussion (within 5 weeks from Day 1), or prior concussion where there are ongoing symptoms. 5. Presence of current psychiatric condition or psychiatric condition requiring pharmacological management within the last 6 months, presence of current or history of psychosis/schizophrenia and bipolar disorders. 6. A calculated creatinine clearance of less than 80 mL/minute at Screening or Check-In (Day -1) according to the equation using Cockcroft and Gault. 7. Liver function tests showing values for alanine transaminase (ALT) or aspartate transaminase (AST) greater than 1.5 times the upper limit of normal (ULN) at Screening. 8. Evidence or history of clinically relevant (in the opinion of the Investigator) other cardiovascular, pulmonary, neurologic or renal disorders or hepatic, gastrointestinal, oral (difficulty swallowing / taking oral medication), hematological, endocrine, or psychiatric impairment/disorders, making implementation of the protocol or interpretation of the study results difficult, or that would put the subject at risk by participating in the study in the opinion of the Investigator. 9. Have undergone surgery requiring or have received (for any reason) anesthetic within 30 days of Day 1. 10. Use of central nervous system (CNS) depressants including opioids, sedatives, anxiolytics, hypnotics, neuroleptics, phenothiazines, tranquilizers, skeletal muscle relaxants, sedating antihistamines or cimetidine within 30 days of Day 1. 11. Use of macrolide antibiotics (e.g., Erythromycin), azole antifungal agents (e.g., Ketoconazole) or protease inhibitors (e.g., Ritonavir) within 30 days of Day 1. 12. Use of any prescription medication within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and the Medical Monitor (in writing). COVID-19 vaccine within 1 week of Day 1 may be administered. Paracetamol ibuprofen, hormonal contraception may be administered. 13. Use of any over the counter product, herbal product, diet aid, or hormone supplement, with a particular regard to hemp or products containing cannabidiol, within 14 days of Day 1 and for duration of study, unless approved by both the Investigator and Medical Monitor (in writing). Vitamins and dietary supplements and topical preparations may be administered (other than those in the prohibited list). 14. History of severe allergic or anaphylactic reactions, known intolerance, allergy or hypersensitivity reactions to dronabinol. 15. Positive screening test for Human Immunodeficiency Virus (HIV) antibodies, Hepatitis B surface antigen or Hepatitis C antibody. 16. Evidence or history of substance or alcohol abuse (drink more than 4 standard units of alcohol per day or greater or equal to 14 standard units per week), including positive results for the urine drugs of abuse test or a positive alcohol breath test at Screening or at Check-In (Day -1). 17. Unwilling or unable to abstain from recreational drug/substance use, alcohol, from 48 hours before check-in until discharge. 18. Unwilling or unable to abstain from caffeine or other xanthine-containing products from check-in until discharge. 19. Subjects who within the last 3 months (from the screening visit) were smokers or vapers. 20. Consumption of grapefruit, grapefruit juice or any products containing CYP3A4 inhibitors and/or inducers and/or CYP2C9 F inhibitors and/or inducers within 14 days of Day 1 and through to completion of the study. 21. Female subject or female partner of male subject that is pregnant or lactating. 22. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 1 month or 5 half-lives prior to Day 1. 23. Donation or loss of more than 500 mL of blood within 1 month of Day 1 and/or plans to donate blood during the study. 24. Other unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrolment.
Outcome results
None listed