Autosomal Dominant Polycystic Kidney
Conditions
Brief summary
The study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of Oral AL01211 in healthy volunteers
Detailed description
This study is a Phase 1, first in human (FIH), randomized, double-blind, placebo-controlled study of AL01211 in healthy adult participants The study consists of two parts: Part A will investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AL01211 in a single ascending dose escalation study in approximately 40 healthy adult participants. Part B will investigate the safety and tolerability, pharmacokinetics, and pharmacodynamics of AL01211 in a multiple ascending dose escalation study in approximately 40 healthy adult volunteers.
Interventions
DRUGAL01211 or Placebo (Part A)
Five dose groups with doses ranging from 2mg to 60 mg
DRUGAL01211 or Placebo (Part B)
Five dose groups with doses ranging from 2-60 mg daily. Each separate dose given for 14 days
Sponsors
Novotech (Australia) Pty Limited
AceLink Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
For Part A (SAD) and Part B (MAD) To be eligible for the study, participants must meet all of the following inclusion criteria: 1. Healthy male or female volunteers, between 18 and 55 years of age 2. Participants in good health as determined by medical history, physical examination, vital signs, ECG, and clinical laboratory tests. 3. Body Mass Index (BMI) between 20.0 and 34.9 kg/m2 (inclusive). 4. Participants who smoke no more than 2 cigarettes per day or equivalent per week (includes e-cigarettes) can be included in the study but must be willing to abstain from smoking during confinement periods. 5. Participants must have no relevant dietary restrictions, 6. Females must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception from Screening until at least 30 days have passed since study drug administration , including the follow-up period. Double contraception is defined as a condom AND one other form of the following: * Established hormonal contraception (oral contraceptive pills \[OCPs\], long-acting implantable hormones, and injectable hormones) for at least 1 month prior to Screening * A vaginal ring or an intrauterine device \[IUD\] * Documented evidence of surgical sterilization at least 6 months prior to Screening (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) for women or vasectomy at least 90 days prior to Screening for men (with appropriate post-vasectomy documentation of the absence of sperm in semen), provided the male partner is a sole partner. * Women not of childbearing potential must be postmenopausal for ≥ 12 months. Postmenopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL at Screening for amenorrhoeic female participants. Females who are abstinent from heterosexual intercourse will also be eligible. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not considered highly effective methods of birth control. Participant complete abstinence for the duration of the study and for 1 month after the last study treatment is acceptable. Female participants who exclusively are in same sex relationships are not required to use contraception. \- Males must be surgically sterile (\> 90 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a woman of childbearing potential (WOCBP), the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from Screening until at least 90 days have passed since study drug administration, including the follow-up period. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner that includes: OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring, or an IUD. Participants with same sex partners (abstinence from penile-vaginal intercourse) are eligible when this is their preferred and usual lifestyle. WOCBP must have a negative pregnancy test at Screening and Day -1 and be willing to have additional pregnancy tests as required throughout the study. Males must not donate sperm for at least 90 days after the last dose of AL01211. 7. Participants must have the ability and willingness to attend the necessary visits to the CRU. 8. Must sign an informed consent form (ICF) indicating that they understand the purpose of, and procedures required for the study and are willing to participate in the study.
Exclusion criteria
For Part A (SAD) and Part B (MAD) A participant who meets any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the safety and tolerability measures of AL01211 through Adverse Events/Serious Adverse Events in healthy adult participants | Baseline to End of the Treatment assessed up to an average of 90 days | Number of participants with treatment related adverse events as assessed through CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the pharmacokinetics of AL01211 in healthy adult participants | Baseline to End of the Treatment assessed up to an average of 56 days | The following parameters are used for pharmacokinetics: AUC0-last, AUC0-24h |
| Measurement of glucosylceramide in plasma and urine following oral dosing of AL01211 | Baseline to End of the Treatment assessed up to an average of 56 days | Change in glucosylceramide levels |
| Measurement of monosialodihexosylganglioside in plasma and urine following oral dosing of AL01211 | Baseline to End of the Treatment assessed up to an average of 56 days | Change in monosialodihexosylganglioside levels |
Countries
Australia
Outcome results
None listed