None listed
Conditions
Brief summary
This is a randomised, double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD) multi-cohort study to assess the safety and tolerability of SKY-0515 and how this drug acts in the body in healthy volunteers. SKY-0515 may be indicated for use in patients with Huntington’s Disease, but a trial of the drug in healthy volunteers is needed before trials in patients with Huntington's Disease can proceed. Who is it for? You may be eligible for this study if you are a healthy male or female volunteer aged 18 to 70 years of age who has met all inclusion criteria and do not meet any exclusion criteria will be eligible to be enrolled. Study details All healthy volunteer participants who choose to enroll in this study will be assigned by chance to receive either a single dose of SKY-0515 or placebo once daily for 14 days. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood and urine samples for testing. If the drug appears safe, additional participants will be assigned by chance to receive a larger single dose of SKY-0515 or placebo once daily for 14 days, followed by blood and urine testing. This will continue until a maximum safe dose is determined. It is hoped this research will determine the maximum dose of SKY-0515 that can be administered safely without causing severe reactions. Once the dose of SKY-0515 has been determined in healthy volunteers, a trial investigating the safety of SKY-0515 as a treatment for patients with Huntington's Disease may proceed.
Interventions
This is a randomised, double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD) multi-cohort study. This study will be conducted in two distinct participant groups: a SAD and food effect part (Part A) in healthy participants and a MAD part (Part B) in healthy participants.
Part A (Single ascending oral dose) in up to 48 healthy male and female participants over 5 dose escalation cohorts (8 participants per cohort) plus 1 food effect cohort (8 participants). T
This is a randomised, double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD) multi-cohort study. This study will be conducted in two distinct participant groups: a SAD and food effect part (Part A) in healthy participants and a MAD part (Part B) in healthy participants. Part A (Single ascending oral dose) in up to 48 healthy male and female participants over 5 dose escalation cohorts (8 participants per cohort) plus 1 food effect cohort (8 participants). The starting dose for Cohort 1 will be 1 mg up to a maximum of 16 mg SKY-0515 or placebo. Subsequent Cohorts 2 - 5, dose levels are to be confirmed by the Safety Review Committee (SRC) based on safety, tolerability and any available pharmacokinetic (PK) results from preceding cohorts. Cohorts 1 to 5 will receive a single oral dose administration of SKY-0515 or placebo on Day 1. For each participant enrolled in Cohorts 1 - 5, the confinement period will commence on Day -1, with dosing on Day 1 and discharge on Day 4. Participants will return to the clinic for their end of study (EoS) visit on Day 8 (±2 days). Part A (Food Effect) in healthy male and female participants Cohort 6 (food effect) a fed or fasted, 2-period, open label, crossover design, 8 healthy adult participants will be randomised to one of 2 treatment sequences (AB/BA), and will receive 2 oral dose administrations of SKY-0515, being a single dose each on Day 1 and 8. Dose level to be selected based on safety, tolerability and any available PK results from Cohorts 1 to 5. In Period 1, participants in treatment sequence AB will receive SKY-0515 following a ten hour fasting period while participants in treatment sequence BA will receive SKY-0515 thirty minutes after commencing a standard high calorie breakfast. A standard high fat, high calorie meal includes: Two eggs fried in butter, Two rashers of bacon, Two slices of toast with 16 g butter per slice, 125 g of hash browns, 240 mL of full cream milk. This high fat (50% of total caloric intake) high calorie (800-1000 calories) test meal derives approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively. In Period 2, participants in treatment sequence AB will receive SKY-0515 under fed conditions while participants in treatment sequence BA will receive SKY-0515 under fasted conditions . Dose administration between periods will be separated by washout period of at least 7 days (and maximum of 10 days). For each participant enrolled in Cohort 6, the confinement period will commence on Day -1 with dosing on Days 1 and 8 with discharge on Day 15. Part B (Multiple ascending oral dose) may commence following completion of at least 2 cohorts in Part A: Up to 32 healthy male and female participants over 4 dose escalation cohorts (8 participants per cohort)) with final dose levels to be determined by the SRC based on safety, tolerability and any available PK results from the preceding cohorts. A single oral dose will be administered of SKY-0515 or placebo once daily (QD) on Days 1 to 14 (inclusive), 14 doses total. On Day 2, the second dose will be administered the morning (approximately 24 hours [± 1 hour]) after the first dose, i.e., the morning of Day 2. All subsequent doses will be administered approximately every 24 hours (± 1 hour relative to first dose on Day 1), up to and including the morning of Day 14. For each participant enrolled in Part B Cohort 7, the confinement period will commence on Day -1 and discharge on Day 17. Participants will return to the clinic for their EoS visit on Day 21 (±2 days). For each participant enrolled in Part B Cohorts 8, 9, and 10 the confinement period will commence on Day -1 to Day 21. The SRC will also review the safety and PK data after the first MAD cohort and Cerebrospinal Fluid samples will also be taken from participants enrolled in Cohorts 9 and 10. Adherence to Intervention will be managed via recording in appropriate drug accountability records.
Sponsors
Skyhawk Therapeutics, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Volunteers will be included in Part A and B of the study only if they satisfy all the following criteria: 1. Must have given written informed consent, before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects. 2. Healthy male or female, aged between 18 and 70 years, inclusive at screening. 3. Body mass index (BMI) of 18 to 35 kg/m2, inclusive, with body weight greater than or equal to 50.0 kg and < 130.0 kg. 4. Participant is medically healthy (in the opinion of the Investigator), as determined by pre-study medical history and without CS abnormalities 5. Female participants must be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or, if of child-bearing potential: a. Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on Day -1. b. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the last dose of study drug. c. If not exclusively in a same-sex relationship or abstinent as a committed lifestyle, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception) from one month prior to screening until at least 30 days after the last dose of study drug. Participants who choose true abstinence during study participation will be considered for study participation even if this is not in line with their typical lifestyle. 6. Male participants must: a. Agree not to donate sperm from the time of signing consent until at least 180 days after the last dose of study drug. b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception for their partner from the time of signing consent until at least 180 days after the last dose of study drug). 7. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
Exclusion criteria
Volunteers will be excluded from Part A and B of the study if there is evidence of any of the following: 1. Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications. 2. Suffers from frequent or recurrent infections (defined as greater than or equal to 3 recurrent or separate occurrences in the 12 months preceding first study drug administration or 2 recurrent or separate occurrences in the 6 months preceding first study drug administration). 3. Active malignancy and/or any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma or low grade cervical intraepithelial neoplasia). 4. Evidence of clinically relevant immunosuppression, including (but not limited to), immunodeficiency conditions such as common variable hypogammaglobulinemia. 5. History of hypersensitivity reaction, anaphylaxis or other CS reactions or known allergy to the study drug or its ingredients. 6. Presence or history of cardiovascular disease (including unstable angina, myocardial infarction, chronic heart failure). 7. History of any CS disorder, including haematologic, pulmonary, hepatic, renal, GI, connective tissue disease, uncontrolled endocrine/metabolic, neurologic (including seizures, strokes, brain tumours), and psychiatric diseases, or any disorder that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug. 8. Presence or having sequelae of GI, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 9. History of surgery or hospitalisation within 12 weeks prior to screening, or surgery planned during the study. 10. Lack of suitable veins for multiple venepunctures/cannulations as assessed by the Investigator or delegate at screening or Day -1. 11. Participant has significant (> 10%) weight gain or loss between screening and Day -1. 12. Participant has donated blood/blood products or experienced significant blood loss within 3 months prior to the first dose administration. 13. Any clinically relevant laboratory finding or medical condition that could place the subject at risk for participation in the study, in the opinion of the Investigator. 14. Regular consumption of >10 standard alcoholic drinks/week where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], 30 mL spirit [40% Alc/Vol]), and/or participant is unwilling to abstain from alcohol while confined to the study clinic. 15. Participant is unwilling to abstain from smoking for at least 48 hours prior to check-in (Day -1) and while confined to the study clinic. 16. Participant is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study. 17. Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results. 18. Any other condition or prior therapy that in the opinion of the Investigator (or delegate) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
Outcome results
None listed