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Trial registered on ANZCTR


Registration number
ACTRN12625000082404
Ethics application status
Approved
Date submitted
3/12/2024
Date registered
24/01/2025
Date last updated
24/01/2025
Date data sharing statement initially provided
24/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
An Open-Label, Crossover, Relative Bioavailability Study Comparing Tablet and Capsule Formulations of SKY-0515 in Healthy Volunteers
Scientific title
An Open-Label, Crossover, Relative Bioavailability Study Comparing Tablet and Capsule Formulations of SKY-0515 in Healthy Volunteers
Secondary ID [1] 313205 0
SKY-0515-003
Universal Trial Number (UTN)
Trial acronym
SKY-0515-003
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington’s Disease 335499 0
Condition category
Condition code
Neurological 332060 332060 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, open-label, single-centre, safety, tolerability, and pharmacokinetic (PK) study evaluating two oral formulations of SKY-0515 in healthy volunteers. The study is a randomized, two-period, two-sequence, complete crossover design comparing capsule formulation to tablet formulation.

Healthy adult participants will be enrolled and randomized to one of two treatment sequences, SKY-0515 as a capsule formulation (Treatment A) or tablet formulation (Treatment B). A total of 16 participants will be enrolled across 2 treatment sequences (AB/BA). Each treatment sequence will enrol 8 participants..

Participants will receive single doses of 8 mg SKY-0515 as a capsule formulation (Treatment A) or tablet formulation (Treatment B) on Day 1 and Day 9, depending on their treatment sequence assignment. On Day 1 (Period 1), participants in treatment sequence AB will receive SKY-0515 as a capsule formulation while participants in treatment sequence BA will receive SKY-0515 as a tablet formulation. On Day 9 (Period 2), participants in treatment sequence AB will receive SKY-0515 as a tablet formulation while participants in treatment sequence BA will receive SKY-0515 as a capsule formulation. Dose administration between periods will be separated by washout period of 8 days.

Participants will be discharged from site after the last PK sample has been collected on Day 16, except in the case of adverse event (AE) required to be followed to resolution at the Principal Investigator (PI) discretion.

Adherence to the intervention will be done via supervised drug administration.
Intervention code [1] 329779 0
Treatment: Drugs
Comparator / control treatment
SKY-0515 8 mg will be administered as a capsule (Treatment A)
Control group
Active

Outcomes
Primary outcome [1] 339659 0
To compare the PK parameters of a single oral dose of SKY-0515 as a single tablet formulation versus single capsule formulation in the fasted state
Timepoint [1] 339659 0
In Period 1, blood plasma samples will be collected via venipuncture at the following timepoints:
Pre-dose Day 1, post dose at 0.5hrs, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, Day 2 at 24hrs and 36hrs post-dose, Day 3 at 48hrs post-dose, Day 4 at 72hrs post-dose, Day 5 at 96hrs post dose, Day 6 at 120hrs post dose, Day 7 at 144hrs post dose and Day 8 at 168hrs post dose.

In Period 2, blood plasma samples will be collected via venipuncture at the following timepoints:
Pre-dose Day 9, post dose at 0.5hrs, 1hr, 2hrs, 3hrs, 4hrs, 6hrs, 8hrs, 12hrs, Day 10 at 24hrs and 36hrs post-dose, Day 11 at 48hrs post-dose, Day 12 at 72hrs post-dose, Day 13 at 96hrs post dose, Day 14 at 120hrs post dose, Day 15 at 144hrs post dose and Day 16 (End of Study (EOS)/Early Termination Visit (ETV)) at 168hrs post dose.
Secondary outcome [1] 440783 0
To determine the safety and tolerability of a single oral dose of SKY-0515 as a tablet and capsule formulation
Timepoint [1] 440783 0
Adverse events - will be graded using the most current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed daily until Day 16 post-first dose (EOS/ETV).

Vital signs - Vital signs include blood pressure and heart rate measured using sphygmomanometer, respiratory rate by manual breath count and temperature by tympanic thermometer. In period 1, vital signs will be obtained at Screening and Day -1, pre-dose Day 1 and 1hr and 8hrs post-dose on Day 1, Day 2 at 24hrs post dose, Day 3 at 48hrs post dose, Day 4 at 72hrs post dose and Day 8 at 168hrs post dose. In period 2, Vital signs will be obtained in triplicate pre-dose Day 9 and 1hr and 8hrs post-dose on Day 9, Day 10 at 24hrs post dose, Day 11 at 48hrs post dose, Day 12 at 72hrs post dose and Day 16 (EOS/ETV) at 168hrs post dose.

ECG - In period 1, 12-lead ECG recordings will be obtained in triplicate at Screening and Day -1, pre-dose on Day 1, 8hrs post-dose on Day 1 and Day 2 at 24hrs post dose. In period 2, 12-lead ECG recordings will be obtained in triplicate pre-dose on Day 9, 8hrs post-dose on Day 9, Day 10 at 24hrs post dose and Day 16 (EOS/ETV) at 168 hrs post dose.

Clinical laboratory evaluations (haematology, chemistry, coagulation and urinalysis) - Blood and urine samples will be collected at Screening and Day -1, pre-dose on Day 1, Day 2 at 24hrs post dose, Day 3 at 48hrs post dose, pre dose on Day 9, Day 10 at 24 hours post dose, Day 11 at 48 hrs post dose and Day 16 (EOS/ETV) at 168 hrs post dose.

Eligibility
Key inclusion criteria
1. Must have given written informed consent before any study-related activities are performed and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
2. Adult males and females, 18 to 70 years of age (inclusive) at screening.
3. Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 35.0 kg/m2, with a body weight greater than or equal to 50.0 kg and less than 130.0 kg at screening.
4. Medically healthy (in the opinion of the PI or delegate), as determined by pre-study medical history, and without CS abnormalities including the following:
a. Physical examination without any clinically relevant findings;
b. Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after resting for 5 minutes in a supine or semi-supine position.
c. Pulse rate in the range of 45 to 100 bpm after 5 minutes resting in a supine or semi-supine position.
d. Body temperature (tympanic), between 35.5°C and 37.7°C (inclusive).
e. ECG without CS abnormalities including QT interval corrected using the Fredericia forrmula (QTcF) less than 450 msec for male participants and less than 470 msec for female participants.
f. No CS findings in chemistry, hematology, coagulation, and urinalysis tests (in the opinion of the PI or delegate).
g. Neutrophil count greater than or equal to 2x10^9/L, platelets count greater than or equal to 150x10^9/L and reticulocyte count greater than or equal to 0.2% of total red blood cells count.
5. Participant is willing to refrain from consuming food or beverages containing caffeine and/or xanthene products, from at least 24 hours prior to dosing on Day 1 and Day 9, and until 24 hours after each dose.
6. Female volunteers:
a. 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
b. If of child-bearing potential, must:
i. Have a negative pregnancy test at the screening visit and on admission to the study site on Day-1.
ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 37 days after the last dose of study drug.
iii. If not exclusively in a same-sex relationship or abstinent as a committed lifestyle or if abstinent from 30 days prior to screening and unwilling to remain abstinent until at least 37 days after the last dose of study drug, must agree to use adequate contraception (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 37 days after the last dose of study drug.
7. Male volunteers:
a. Must agree not to donate sperm between signing the consent form and 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 combined with use of a highly effective method of contraception between signing the consent and at least 180 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom between signing the consent form and at least 180 days after the last dose of study drug .
8. Have suitable venous access for blood sampling.
9. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Volunteers will be excluded from the study if they meet any of the following criteria:
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. Prescence or having sequelae of GI, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs (prior gall bladder and/or appendix removal is not exclusionary if the procedure was undertaken greater than or equal to 3 months prior to study drug administration; if less than 3 months, history of such procedures may still be considered not exclusionary if it is deemed appropriate by the PI or delegate).
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 venipunctures/cannulations as assessed by the PI or delegate at screening or Day -1.
11. Volunteer has significant (greater than 10%) weight gain or loss between screening and Day -1.
12. Volunteer has donated blood/blood products or experienced significant blood loss within 3 months prior to the first dose administration.
13. Laboratory results at screening that indicate inadequate renal function (estimated creatinine clearance of less than 60 mL/min calculated by the Cockcroft and Gault formula).
14. Liver function test results elevated more than 1.5-fold above the Upper limit of normal (ULN) for gamma glutamyl transferase (GGT), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI, if the levels are unaccompanied by clinical signs and are determined to be normal variants.
15. Liver function tests outside the normal range for bilirubin (more than 1.5-fold above the ULN for total bilirubin).
16. Any clinically relevant laboratory finding or medical condition that could place the participant at risk for participation in the study, in the opinion of the PI.
17. Use of any vaccinations within 14 days (within 4 weeks for live virus vaccines) prior to the first study drug administration.
18. Use of any prescription medication or over-the-counter medication/supplements/herbal medications within 7 days prior to the first dose of study drug. Exceptions include:
a. Contraception,
b. Antihistamines,
c. Occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days) or ibuprofen (doses of 400 mg up to every 6 hours or 1.2 g per day maximum for no more than 3 consecutive days),
d. Low doses of multivitamins,
19. Use of St. John’s Wort (hypericin) within 30 days prior to first dose of study drug.
20. Concurrent enrolment in another clinical study, or participation in another clinical study within 30 days or 5 half-lives of the IP (whichever is longer) prior to screening.
21. Regular consumption of greater than 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 volunteer is unwilling to abstain from alcohol while confined to the study site.
22. Positive alcohol breath test at screening or upon admission to the study site on Day -1.
23. Positive urine drugs of abuse test at screening or upon admission to the study site on Day -1.
24. Volunteer has a positive cotinine test upon admission to the study site on Day -1.
25. Volunteer smokes 10 or more cigarettes or equivalent (see note below) per week, and/or volunteer is unwilling to abstain from smoking for at least 48 hours prior to check-in (Day -1) and while confined to the study site.
26. Volunteer is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study.
27. Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the volunteers inclusion in the clinical study or evaluation of the clinical study results.
28. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
29. Any other condition or prior therapy that in the opinion of the PI (or delegate) would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
All study participants who sign an informed consent form (ICF) will receive a unique sequential number (i.e., a screening number).

Participants who meet the study eligibility criteria will be assigned a randomisation number pre-dose on Day 1, which corresponds to a treatment sequence (Sequence AB or Sequence BA). The allocation to Sequence AB or Sequence BA will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule. Randomisation numbers assigned will be in accordance with this randomisation schedule. The randomisation schedule will be prepared by a statistician.

The PI (or delegate) will provide the randomisation number assigned to a participant to the personnel responsible for dispensing study drug who will have a copy of the randomisation schedule. The personnel will dispense the study drug allocated to that randomisation number as specified on the randomisation schedule.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-availability
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/03/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 27247 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 43328 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 317649 0
Commercial sector/Industry
Name [1] 317649 0
Skyhawk Therapeutics, Inc.
Country [1] 317649 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Skyhawk Therapeutics, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 319965 0
Commercial sector/Industry
Name [1] 319965 0
Avance Clinical Pty Ltd
Address [1] 319965 0
Country [1] 319965 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316348 0
Bellberry Human Research Ethics Committee L
Ethics committee address [1] 316348 0
https://bellberry.com.au/
Ethics committee country [1] 316348 0
Australia
Date submitted for ethics approval [1] 316348 0
18/12/2024
Approval date [1] 316348 0
21/01/2025
Ethics approval number [1] 316348 0

Summary
Brief summary
Study Hypothesis
This study aims to compare how the body absorbs two different forms of the drug SKY-0515 tablet and capsule in healthy volunteers. Based on preclinical data, we expect the exposures of these two formulations in healthy volunteers to be similar. Skyhawk will eventually use the tablet formulation to treat Huntington's patient.

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
The study is designed to compare the relative bioavailability of single dose oral administration of 2 formulations of SKY-0515, tablet solid dosage form to capsule formulation, in healthy volunteers. All healthy volunteer participants who choose to enroll in this study will receive 8 mg of SKY-0515 which will be administered orally as either a capsule (Treatment A) or a tablet (Treatment B). On Day 1 (Period 1), participants in treatment sequence AB will receive SKY-0515 as a capsule formulation while participants in treatment sequence BA will receive SKY-0515 as a tablet formulation. On Day 9 (Period 2), participants in treatment sequence AB will receive SKY-0515 as a tablet formulation while participants in treatment sequence BA will receive SKY-0515 as a capsule dose. Dose administration between periods will be separated by washout period of 8 days.

All participants will have their vital signs (heart rate, blood pressure, temperature and respiratory rate) and ECGs checked, and will provide blood and urine samples for testing to ensure SKY-0515 is safe and well tolerated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137610 0
Dr Michele de Sciscio
Address 137610 0
CMAX Clinical Research Pty Ltd, Ground Floor, 21-24 North Terrace, Adelaide, South Australia, 5000
Country 137610 0
Australia
Phone 137610 0
+61 422 447 902
Fax 137610 0
Email 137610 0
[email protected]
Contact person for public queries
Name 137611 0
Dr Michele de Sciscio
Address 137611 0
CMAX Clinical Research Pty Ltd, Ground Floor, 21-24 North Terrace, Adelaide, South Australia, 5000
Country 137611 0
Australia
Phone 137611 0
+61 422 447 902
Fax 137611 0
Email 137611 0
[email protected]
Contact person for scientific queries
Name 137612 0
Dr Michele de Sciscio
Address 137612 0
CMAX Clinical Research Pty Ltd, Ground Floor, 21-24 North Terrace, Adelaide, South Australia, 5000
Country 137612 0
Australia
Phone 137612 0
+61 422 447 902
Fax 137612 0
Email 137612 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.