Not Yet RecruitingPhase 1ACTRN12625001215415

A study to assess safety, tolerability, and pharmacokinetics of RTX-001/101 in healthy adults. Part 1A and Part B healthy participants only

A Randomized, Placebo Controlled, Double-Blind, Single-Ascending Dose and Multiple-Ascending Dose First-in-Human Study to Investigate the Safety, Tolerability, and Pharmacokinetics, of Orally Administered RTX-001/101 in Healthy Adult Subjects

Sponsor

Repeat Therapeutics Pty Ltd

Enrollment

104 participants

Start Date

Nov 4, 2025

Study Type

Interventional

Conditions

Amyotrophic Lateral Sclerosis

Summary

A Phase 1, First-in-Human, Single and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral administration of RTX-101, RTX-010 and RTX-111 in Healthy Subjects. The current study is the first clinical co-administration of combinations of RTX-101, RTX-010 and RTX-111 to be conducted in healthy adult subjects. The study includes Part 1A: single ascending dose (SAD) and Part 1B: multiple ascending dose (MAD).

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria12

Must be able to provide written, personally signed and dated informed consent to participate in the study in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations before completing any study related procedures.
Male or female ages 18 to 65 years, inclusive, at the time of consent.
Relatively good health as determined by the Investigator based on review of medical history, physical examination, ECG, vital signs, and clinical laboratory tests.
Body mass index (BMI) 18 to 35 kg/m2 inclusive (BMI = weight (kilograms)/(height [meters]2).
Non-smokers or tobacco/nicotine user (e.g., smokers, electronic cigarettes, vaping, and smokeless tobacco/nicotine products), that are willing to abstain from nicotine use throughout the study (Day-1 through End of Study Follow-up).
Females of childbearing potential must agree to use a highly effective method of contraception from the time of consent through at least 3 months after the last dose of study medication. Highly effective methods of contraception include: intrauterine device, intrauterine system, contraceptive implant, combined injectable contraceptives, hormonal oral contraceptives when used in combination with male condoms. Sexual abstinence, defined as refraining from intercourse, when this is in line with the preferred and usual lifestyle of the participant. Remain exclusively in a same sex relationship, when this is in line with the preferred and usual lifestyle of the participant. Female participants with male partner(s) must utilize highly effective forms of contraception and their male partner(s) must use a male condom. Female participants must refrain from donating ova from 3 months after administration of the last dose of study drug.
Females of nonchildbearing potential must be postmenopausal (defined as a minimum of 12 consecutive months of spontaneous amenorrhea) or surgically sterile (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral tubal occlusion). Females of nonchildbearing potential are exempt from contraception requirements.
Males who are sexually active and whose partners are females of childbearing potential must agree to use male condoms from the time of consent through 3 months after administration of the last dose of study drug, and their partners must be willing to use a highly effective method of contraception from screening through 3 months after administration of the last dose of study drug. Males must agree not to donate sperm from screening through 3 months after administration of the last dose of study drug.
Able to refrain from consuming xanthine containing beverages and food (e.g., coffee, tea, cola, energy drinks and dark chocolate) from 24 hours prior admission to the clinic until the End of Study visit.
Must refrain from intensive physical exercise from 48 hours prior admission to the clinic until the End of Study visit.
Must not take any prescription with the exception of contraceptives or over-the-counter medications, herbal remedies, or food supplements during the study unless otherwise approved by the Investigator.
Must be fluent in English and have a degree of understanding sufficient to communicate suitably with the Investigator and the study coordinator.-

Exclusion Criteria29

Any of the following medical conditions:
a. Any active or serious medical condition which could interfere with the participant's safety during the trial,
b. History or presence in the past 5 years of gastrointestinal, hepatic or renal disease (eGFR > 75mL/min/1.73m2 or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
c. Positive tests for HIV, hepatitis B or hepatitis C.
d. Participants must not have a history of seizure disorder.
e. Previous malignant disease (except basal cell carcinoma of skin and cervical carcinoma in situ/dysplasia).
f. History of thyroid impairment or dysfunction and/or require medical intervention for thyroid impairment/dysfunction.
Must not have a history of organic heart disease including coronary artery disease, myocardial infarction, angina, clinically significant abnormal ECGs, QTcF interval > 450 msec for males and >470 msec for females, congestive heart failure, valvular heart disease and congenital heart disease.
Must not have screening or baseline: systolic blood pressure (SBP) > 139 mmHg, diastolic blood pressure (DBP) > 89 mmHg, and resting heart rate (HR) > 90 BPM. Vital signs may be repeated once at the Investigator’s discretion.
Known gout and/or treatment required gout and/or hyperuricemia.
Use of concomitant medications that prolong the QT/QTc interval or triptan medications for migraine headaches.
Must not have abnormal iron storage including haemochromatosis
Active primary psychiatric disorders based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition,
Psychiatric hospitalization within 12 months of screening date.
Must not have a history of moderate to severe substance use disorder according to DSM-5-TR criteria currently or within one year prior to enrolment, excluding nicotine.
Must not test positive for a substance of abuse or have a positive alcohol breath test at the time of screening or check in.
Must not have a history of, or current, dysphagia or other swallowing difficulties that, in the opinion of the investigator,
History of excessive daily consumption of caffeine containing drinks (i.e., > 400 mg/day of caffeine or 4-5 cans (300 ml to 355 ml) of cola beverages.
Positive pregnancy test at screening or check in or is breastfeeding/lactating.
Any history of drug or other significant allergy.
Symptoms or history suggestive of a recent systemic illness or febrile illness within 7 days prior to check in based on the Investigator’s discretion.
Donation of one or more units of blood within 60 days, plasma within 30 days prior to the screening or platelet donation within 60 days prior to screening.
Cannot tolerate venipuncture or has poor venous access
Use of any prescription medication (excluding contraceptives) within 7 days or 5 half-lives prior to admission to the clinic on Day -1 through the End of Study visit.
Use of over-the-counter medications, herbal and nutritional supplements including St. John’s Wort within 4 days or 5 half-lives prior to admission to the clinic on Day -2.
Has taken other investigational drug or participated in any clinical study 30 days prior to the dosing or is currently participating in another clinical study.
Clinically significant laboratory (blood or urine) abnormality as defined by the investigator. Liver enzymes (Total Bilirubin, AST/ALT, ALP, GGT) may not be greater than 1.5X the upper limit of normal (ULN) at baseline.
Unwilling or unlikely to comply with the requirements of the study.
Unable to commit to participating in the entire estimated 7 (±2 days) for Part 1A and (14 (±4) days for Part 1B of the trial

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Interventions

This is a first-in-human (FIH), multi-centre, double-blind, placebo-controlled, randomized, SAD, MAD study of RTX-101, RTX-010 and RTX-111 conducted in healthy adult participants and adult patients with C9orf72-ALS designed to evaluate the safety, tolerability, and PK of RTX-101, RTX-010 and RTX-111. The treatments RTX-101 (comprises of 2 different medications), RTX-010 (is only 1 medication) and RTX-111 (comprises of 3 different medications, RTX-101 and RTX-010) are white opaque gelatine capsules. There are 2 parts to the study: Part 1 is known as Part 1A and Part 2 is known as Part 1B. In all cohorts of Part 1A (Single Ascending Dose - SAD) and Part 1B (Multiple Ascending Dose - MAD), the participants will register their interest in the study and the potential dates which are suitable for taking part in the study. The dates which are advised by the CMAX team will identify which cohort each participant will be taking part in. Dosing in all cohorts of SAD and MAD will be administered orally. Participants will be instructed to swallow the capsule (s) whole and the site will check their mouth afterwards to ensure they have swallowed the capsule (s). The commencement of dosing in SAD Arm A and SAD Arm B cohorts may overlap due to the safety of different study drugs being investigated Part 1A: Single ascending dose (SAD) in healthy volunteers. Eight participants will be dosed in each cohort of Part 1A. Part 1A Cohort 3 will have 2 periods where the same participants will take part in each period. SAD Cohort 3, Both periods in Cohort 3 will follow the same schedule as for Cohorts 1, 2, & 4, and that Period 2 will commence after a washout period of at least 14 days. There will be a total of n= 64 participants dosed in Part 1A (SAD) SAD Arm A: RTX-101 or placebo (3:1 Randomization Ratio) n= 32 participants will take part in Arm A Cohort 1: Participants will receive oral doses of RTX-101 (1 x 500mg capsule and 1 x 300mg capsule) or placebo (1 x 500mg and 1 x 300mg capsule) Cohort 2: Participants will receive oral doses of RTX-101 (2 x 500mg and 1 x 300mg capsule) or placebo (2 x 500mg and 1 x 300mg capsule) Cohort 3: Participants will receive oral doses of Period 1 RTX-101 (4 x 500mg and 1 x 300mg capsule) or placebo (4 x 500mg and 1 x 300mg capsule) Cohort 3: Participants will receive oral doses of Period 2 RTX-101 (4 x 500mg and 1 x 300mg capsule) or placebo (4 x 500mg and 1 x 300mg capsule) (mixed in apple-sauce), Cohort 4: Participants will receive oral doses of RTX-101 (6 x 500mg and 1 x 300mg capsule) or placebo (6 x 500mg and 1 x 300mg capsule) SAD Arm B: RTX-010 or Placebo (3:1 Randomisation Ratio) n= 24 participants will take part in Arm B. Cohort 5: Participants will receive oral doses of RTX-010 100mg capsule or placebo 100mg capsule Cohort 6: Participants will receive oral doses of RTX-010 200mg capsule or placebo 200mg capsule Cohort 7: Participants will receive oral doses of RTX-010 300mg capsule or placebo 300mg capsule SAD Arm C: Cohort 8 Participants will receive oral doses of RTX-111 (combination of Arm A and B) or Placebo (combination of Arm A and Arm B) (3:1 Randomization Ratio) n=8 participants will take part in Arm C. The dose levels of RTX-111 will be based on the Cohort 1 to 7 safety data and PK data (data from the blood samples to determine the levels of the drugs in their blood). There is a Safety Review Committee will review all the data to determine the levels. Part 1B: Multiple ascending dose (MAD) in healthy volunteers. Dose once daily from Day 1 to Day 7. A total of n=40 participants will be dosed in Part 1B (MAD) MAD Arm A: 16 participants will be dosed in this Arm Participants will receive oral doses of RTX-101 or Placebo (3:1 Randomization Ratio) RTX-101 dosage to be determined based on Part 1A cohorts. There is a Safety Review Committee who will review all the data to determine the levels. MAD Arm B: 16 participants will be dosed in this Arm Participants will receive oral doses of RTX-010 or Placebo (3:1 Randomization Ratio) RTX-010 dosage to be determined based on Part 1A cohorts. There is a Safety Review Committee who will review all the data to determine the levels. MAD Arm C: n=8 participants will take part in this arm. Participants will receive oral doses of RTX-111 or Placebo (3:1 Randomization Ratio) RTX-111 - dosage to be determined based on the Part 1A cohorts. There is a Safety Review Committee who will review all the data to determine the levels.