None listed
Conditions
Brief summary
This study includes 4 single ascending dose cohorts (fasted), 1 fasted/fed food effect cohort and 5 fasted multiple ascending dose cohorts. The main purpose is to examine the safety and tolerability of RTR242 following single and multiple ascending doses in healthy adult subjects. Participants will be contacted by telephone 28 days after their last dose of study drug for safety follow up.
Interventions
The study will be examining RTR242, an oral liquid solution. The study drug is a powder that will be dissolved in liquid (between 6.25 and 25ml, depending on the dose). The study drug will be administered with 240ml (approximately 1 cup) of water by each participant, under the supervision of site staff, who will perform checks of the mouth.
Participants who enrol in the single ascending dose (SAD) portion of the study will be enrolled in 1 of 5 SAD cohorts (8 participants per cohort; 6 receiv
The study will be examining RTR242, an oral liquid solution. The study drug is a powder that will be dissolved in liquid (between 6.25 and 25ml, depending on the dose). The study drug will be administered with 240ml (approximately 1 cup) of water by each participant, under the supervision of site staff, who will perform checks of the mouth. Participants who enrol in the single ascending dose (SAD) portion of the study will be enrolled in 1 of 5 SAD cohorts (8 participants per cohort; 6 receiving RTR242 and 2 participants receiving placebo). - SAD Cohorts 1, 2, 4 and 5 will receive a single dose of RTR242 or placebo under fasted conditions. - SAD Food Effect (FE) Cohort 3 will receive a single dose of RTR242 or placebo on Day 1 (under fasted conditions) and on Day 8 approximately 30 minutes after consuming a high fat meal (about 800-1000 calories, approximately 15% protein, 25% carbohydrates and 60% fat). The doses planned for the SAD cohorts range from 50mg up to a maximum of 800mg. Cohort 1 will receive 50mg of RTR242, with each sequential cohort's dose increasing up to 100% from the previous cohort, based on the outcomes/review of the safety data by the Safety Review Committee (SRC) (i.e. Cohort 1 will receive 50mg RTR242, Cohort 2 will receive up to 100mg RTR242, FE Cohort 3 will receive up to 200mg RTR242, etc.). The multiple ascending dose (MAD) part of the study may commence once the SRC has reviewed the data obtained from SAD Cohort 3 (Food Effect) fasted period. Participants who enrol in one of the SAD cohorts will not take part in the MAD part of the study. Participants who enrol in the MAD portion of the study will be enrolled in 1 of 5 MAD cohorts. - Cohorts 6, 7, 8 and 9 (8 participants per cohort; 6 participants receiving RTR242 and 2 participants receiving placebo) will receive daily doses of RTR242 (up to a maximum of 800mg per day) or placebo for 6 days. - Cohort 10 (4 participants) will receive up to 800mg of RTR242 daily for 6 days. The starting dose of RTR242 to be tested in Cohort 6 will be the same dose that was tested in SAD Cohort 2. The dose level to be tested in Cohort 7, 8 and 9 will increase up to 100% from the previous cohort, based on the outcomes/review of the safety data by the Safety Review Committee (i.e. if Cohort 6 receives 100mg RTR242, Cohort 7 will receive up to 200mg RTR242, Cohort 8 would receive up to 400mg RTR242, etc.). The dose level for Cohort 10 will be chosen following the review of all the MAD data. The maximum dose in the MAD part of the study will not exceed the maximum dose achieved in the SAD cohorts.
Sponsors
Retro Au Pty Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
- Aged 18-65 years of age inclusive at the time of informed consent; - Body mass index (BMI) between 18 and 32.0 kg/m2, inclusive; - Female participants of non-child-bearing potential (either post-menopausal for at least 12 months with no menses and as confirmed by Follice Stimulating Hormone (FSH) level greater than 40 IU/L at Screening, or surgically sterilized by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or females of child-bearing potential who must agree to use one of the following appropriate contraceptive methods from informed consent until at least 90 days after the last dose of assigned study drug: a. Complete abstinence from heterosexual intercourse in line with their preferred and usual lifestyle OR b. Male condom in combination with a highly effective contraceptive method (established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); bilateral tubal ligation; vasectomized male partner provided they are the sole partner. - Male participants who agree to use one of the following appropriate contraceptive methods, and agree to refrain from sperm donation, from informed consent until at least 90 days after the last dose of assigned study drug: a. Complete abstinence from heterosexual intercourse in line with their preferred and usual lifestyle OR b. Male condom in combination with the female partner using a highly effective contraceptive method (established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); bilateral tubal ligation; vasectomy), OR c. Exclusively with a female partner of non-childbearing potential (either post-menopausal for at least 12 months, or surgically sterilized by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) - Social smokers (using no more than 5 cigarettes or equivalent tobacco/nicotine-containing products per week on average) who are willing to abstain from these products within 48 hours before check-in (Day -1) and throughout confinement; - Healthy as defined by no clinically significant findings by the Investigator/delegate in review of medical history, physical examination, vital sign measurements, 12-lead ECG and clinical laboratory results from Screening through to pre-dose Day 1 assessments. Repeat assessments are permitted at the discretion of the PI/delegate; - Conventional 12-lead ECG recorded in triplicate (the mean of triplicate measurements will be used to determine eligibility) consistent with normal cardiac conduction and function during Screening - Negative nicotine, drug, and alcohol tests during Screening and check-in (Day -1) and willing to abstain from alcohol/illegal drug use until completion of the EOS/ET visit.
Exclusion criteria
- History of substance misuse in the opinion of the Investigator, or alcohol misuse defined as regular consumption of > 10 standard drinks per week or > 4 standard drinks on any given day, within 12 months prior to Day 1 (1 standard drink being equivalent to 100mL of wine, 30 mL of spirits or 285 mL of mid-strength beer or cider); - History of suicidal behavior or suicidal ideation; as determined by medical history or by clinically significant findings on the baseline Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening; - Known active hepatitis B or C infection, human immunodeficiency virus (HIV) infection, or has known immune deficiency disease at Day 1; - Use of any prescription drug within 30 days prior to Day 1, except for hormonal contraceptives (oral contraceptive pills or implant) for females of child-bearing potential which have been in stable use for at least 2 months; - Use of over-the-counter (OTC) products including St John’s Wort within 14 days prior to Day 1 through discharge (except for vitamin supplements or paracetamol up to 2 g/day, natural food supplements, garlic as a supplement); - Vaccines within 30 days before Day 1, and/or planned vaccination through the EOS/ET visit; - Blood or plasma donation within the past 2 months prior to Day 1, and/or receipt of blood transfusion within 1 month before Day 1; - Presence or history of any clinically significant condition/disorder (as determined by the Investigator) including but not limited to: allergies, asthma, angioedema, pulmonary disease, bronchospasm, ulcer disease, gastrointestinal (GI), GI bleeding, coagulation defects, unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, bradycardia, tachycardia, hypotension, hypertension, edema, heart failure, hypokalemia, cardiovascular disease, significant dermatologic diseases or conditions, hematological, neurological, psychiatric, hepatic, or renal disorders, condition that would significantly influence the immune response; or history of infections of unexplained frequency or severity; - Surgical (history of stomach or intestinal surgery or resection) or medical condition (evidence of prior chronic GI inflammatory disease) that would interfere with gastric motility, pH, or absorption that could interfere with the administration of the assigned study drug; - Received systemic treatment for cancer except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast within the 5 years prior to Day 1; - Severe allergy or anaphylaxis to any drug or food; - Use of any investigational drug, investigational device, approved therapy for investigational use or participation in an investigational study within 30 days (or five half-lives of the investigational drug, whichever is longer) prior to Day 1 and/or unwillingness to allow at least 28 days from last dose of assigned study drug before participation in another investigational trial; - Unwilling to abstain from alcoholic beverages/alcohol-containing products and xanthine-based beverages from 48 hours prior to Day -1 until completion of the EOS/ET visit, poppy seed containing foods from 72 hours prior to Day -1 until discharge, or returns a positive urine drug screen or alcohol breath test at Screening or Day -1; - Females who are pregnant, plan to donate ova or become pregnant during the study and/or up to for at least 90 days after the last dose of study drug, or are breastfeeding.
Outcome results
None listed