Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12624001392550
Ethics application status
Approved
Date submitted
17/10/2024
Date registered
25/11/2024
Date last updated
25/11/2024
Date data sharing statement initially provided
25/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety, Tolerability, and Pharmacokinetics of Oral SCY-247 in Healthy Subjects: Part 1-3
Scientific title
A Four-Part, Phase 1, First-in-Human, Single- and Multiple-Ascending Dose and Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral SCY-247 in Healthy Subjects: Part 1-3
Secondary ID [1] 313021 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fungal Infections 335234 0
Condition category
Condition code
Infection 331771 331771 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The current study is the first clinical administration of SCY-247 to be conducted in healthy adult subjects.
It is a 4-part study combining Part 1: single ascending dose (SAD), Part 2: multiple ascending dose (MAD), Part 3: loading and maintenance doses, Part 4: drug-drug interaction. SCY-247 will be provided as 50-mg and 200-mg tablets for oral administration. Part 1,2,3 are placebo-controlled study registered in this form, with Part 4 registered separately.

1. Part 1 (SAD) – up to 7 dosing cohorts:
Cohorts A to G: Single oral doses of SCY-247 (50, 100, 200, 400, 800, 1200, 1600 mg) or placebo will be administered in the fasted state (i.e. no solid food for 8 hours, The 4th dose level will be repeated in the same volunteers after a high-fat meal (30min prior to dosing), after safety of 800 mg (Cohort E) at 24 hours post dose has been confirmed by the PI. A high fat meal will be of 50% fat, 800-1kCal in form of two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes and eight ounces of whole milk.

2. Part 2 (MAD) – up to 5 dosing cohorts:
- Cohorts H to L: Oral doses of SCY-247 (100, 200, 400, 600 and 800 mg) or placebo will be administered once daily for 7 days. Dosing is planned to be in the fasted state i.e. no solid food for 8 hours,

3. Part 3 Loading and maintenance doses – up to 2 dosing cohorts:
- Cohort M: Oral doses of SCY-247 not exceeding 800 mg twice daily on Day 1 and then 800 mg once daily from Days 2 to 7 (maintenance dose).
- Cohort N: Oral doses of SCY-247 not exceeding 800 mg twice daily on Days 1 and 2, and not exceeding 800 mg once daily from Days 3 to 7 (maintenance dose).
Administration of SCY-247 is planned to be in the fasted state but may be changed to administration in fed state if data are reviewed and confirmed by the SRC.

Dose administrators and witness will count the number of tablets to be administered and observe subject being dosed. A mouth check will be performed and check the dose bottle is empty after dosing.
The study duration from screening to post study visit will be approximately 6 weeks for Part 1, approximately 8 weeks for Parts 2 and 3, and approximately 9 weeks for Part 4.

For Parts 1, 2 and 3, subjects will be randomized to treatment (SCY-247 or Placebo) according to a computer-generated randomization schedule. Part 4 is an open-label design. This registration is for Part 1 to Part 3.
Intervention code [1] 329569 0
Treatment: Drugs
Comparator / control treatment
Placebo control agent will be a round coated tablet with Microcrystalline cellulose, mannitol, croscarmellose sodium, magnesium stearate, sodium stearyl fumarate, and colloidal silicon dioxide. A film coating of Opadry II (white film coat).
Control group
Placebo

Outcomes
Primary outcome [1] 339427 0
To evaluate the safety and tolerability of ascending single oral doses of SCY 247 in healthy subjects.

- Incidence and severity of treatment-emergent adverse events (TEAEs) will be assessed for severity and causality (relationship of event to the investigational product) by the study investigator using the specified definitions.
- Changes in clinical laboratory parameters including blood tests for complete blood count. coagulation, serum chemistry, and urinalysis.
- Change in vital signs measurements. Vital signs include measurement of heart rate (HR) respiration rate (RR), systolic and diastolic blood pressure (BP) and body temperature.
- Changes in the electrocardiogram (ECG) findings)

All measures will be assessed as a composite outcome
Timepoint [1] 339427 0
- Adverse events monitored from screening to end of study (EOS-Day 14 for part 1; Day 21 for part2 and 3) post first dose administration.
- Safety Lab parameters from screening to end of study (EOS-Day 14 for part 1; Day 21 for part2 and 3) post first dose administration.
- Vital signs will be assessed from screening to end of study (EOS-Day 14 for part 1; Day 21 for part2 and 3) post first dose administration.
Secondary outcome [1] 439959 0
To evaluate the plasma pharmacokinetics (PK) following single oral administration of SCY 247 in healthy subjects (Part 1).
Timepoint [1] 439959 0

Blood samples will be collected pre dose and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours after SCY-247 first dose administration.
Secondary outcome [2] 440181 0
To assess the effect of a standard high-fat meal on the plasma PK of SCY-247 after a single oral dose of SCY-247 in healthy subjects (Part 1).
Timepoint [2] 440181 0
Blood samples will be collected pre dose and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours after SCY-247 first dose administration.
Secondary outcome [3] 440182 0
To obtain plasma PK data of SCY-247 and potentially metabolite(s) after multiple oral doses of SCY 247 in healthy subjects (Part 2).
Timepoint [3] 440182 0
-Day 1 predose and at 1, 2, 4, 6, 8 and 12 hours after SCY-247 dose administration.
-Days 2 through Day 6: predose and Tmax (Tmax to be determined based on SAD PK data)
-Day 7: predose and at 1, 2, 4, 6, 8, 12, 24, 36, 48 (Day 9), 72 (Day 10), 96 (Day 11) and 120 (Day
12) hours after SCY-247 dose administration on Day 7
Secondary outcome [4] 440187 0
To determine the appropriate loading dose that will achieve target plasma exposure.

Plasma PK data (eg, AUC0 8, AUC0 12, AUC0 24, Cmax, Tmax, and t1/2,) will be determined following single oral dose, and after the last dose for part 3.
Timepoint [4] 440187 0
Blood samples will be collected at following timepoints for cohort M and N-
Cohort M: Predose and at 1,2,4,6,8 hrs after SCY-247 (AM and PM) administration on Day 1 and Day2; Day 3 through Day 6- Predose and Tmax (Tmax to be determined based on prior PK data); Day 7- predose and at 1, 2, 4, 6, 8, 12, 24, 36, 48 (Day 9), 72 (Day 10), 96 (Day 11) and 120 (Day 12) hours after SCY-247 dose administration on Day 7.

Cohort N: Predose and at 1,2,4,6,8 hrs after SCY-247 (AM and PM) administration on Day 1; Days 2 through 6: predose and Tmax (Tmax to be determined based on prior PK data); Day Day 7: predose and at 1, 2, 4, 6, 8, 12, 24, 36, 48 (Day 9), 72 (Day 10), 96 (Day 11) and 120 (Day 12) hours after SCY-247 dose administration on Day 7.
Secondary outcome [5] 440565 0
To assess the cardio dynamic assessment to exclude the relevant effects on ECG parameters by Holter monitoring in Part 1 and Part 2
Timepoint [5] 440565 0
ECG will be checked on Predose and 24hr post dose on Day 1 for cohorts D (period 1, fasted) E, F and G; 2hrs Predose and 24hr post dose on Day 1 and 7 for Cohorts J, K and L.

Eligibility
Key inclusion criteria
1. Subject is a healthy male or female aged between 18 to 50 years, inclusive, at the screening visit.
2. Subject has a Body Mass Index (BMI) <32 kg/m2, inclusive, at the screening visit and body weight between 45.0 kg and 100.0 kg inclusive for females, and between 50.0 kg and 110.0 kg inclusive for males, at the screening visit.
3. Subject is judged to be in good health based on medical history, physical examination, electrocardiogram (ECG), vital sign measurements and laboratory safety testing performed at the screening visit and prior to administration of the initial dose of study drug, in the opinion of the investigator.
4. Subject has been a nonsmoker and/or has not used nicotine or nicotine containing products for at least 6 months; subjects who have not discontinued smoking or the use of nicotine/nicotine containing products within 6 months, but who in the past 3 months have smoked less than equal to 2 cigarettes or equivalent (eg, cigars, vaping, nicotine patches) per week, may be enrolled in the study at the discretion of the investigator.
5. Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
6. Subject is willing to comply with the study restrictions and participate for the full length of the study.
7. Subject does not have any relevant dietary restrictions that could impact their ability to comply with fasting requirements including willing to consume a high-fat meal if participating in Part 1, Cohort D.
8. Females must not be pregnant or lactating, and must use acceptable, highly effective double contraception from Screening until 90 days after study completion, including during the Follow-up period as described in the protocol. Males must be surgically sterile (>30 days since vasectomy with no viable sperm), or if engaged in sexual relations with a WOCBP, either his partner must be surgically sterile (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or an acceptable, highly effective contraceptive method must be used from Screening until study completion, including during the Follow-up period. Males must not donate sperm from the first dose of IP until at least 90 days after the last dose of IP.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Underlying psychological medical condition that, in the opinion of the PI, would make it unlikely for the participant to comply with the protocol or complete the study per protocol.
2. Subject has a history of any illness or clinical findings that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by participation in the study.
3. Subject has a history of fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening.
4. Subject has poor pill swallowing ability.
5. Subject has an estimated creatinine clearance less than equal to 80 mL/min based on the CockcroftGault equation, as follows:
o Estimated creatinine clearance is equal to [(140 – age) x weight in kg] / [72 x serum creatinine in mg/dL] [x 0.85 if female].
Subjects who have an estimated creatinine clearance up to 10% below 80 mL/min may be enrolled in the study at the discretion of the investigator.
6. Subject has risks for QT prolongation including a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds for males and >470 milliseconds for females).
7. Subject has a history of additional significant risk factors for torsade de pointes (e.g., family history of Long QT Syndrome).
8. Subject is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John’s Wort [hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit. There may be certain medications eg paracetamol, vitamins, ibuprofen that are permitted at investigator’s discretion.
9. Subject has a history of stroke, chronic seizures or major neurological disorder.
10. Subject has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory or genitourinary abnormalities or diseases. Subjects with a history of uncomplicated kidney stones or childhood asthma may be enrolled in the study at the discretion of the investigator.
11. Subject has a history of neoplastic disease or any active cancer, except for non-melanoma skin cancer, excised more than 2 years before screening, and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening.
12. Subject has a history of liver disease, including chronic hepatitis, or aspartate aminotransferase (AST), alanine aminotransferase (ALT) and/or Total Bili >1.5 × upper limit of normal (ULN) at Screening. Repeat testing at Screening is acceptable for out-of-range values based on investigator’s discretion.
13. Subject has a history of human immunodeficiency virus (HIV), hepatitis C (HCV) antibodies, and hepatitis B surface antigen (HBsAg).
14. Regular alcohol consumption defined as > 10 standard drinks per week (where 1 standard drink is equal to 360 mL of beer, 45 mL of 40% spirit or a 150 mL glass of wine) or > 4 standard drinks on any single day. Subject is unwilling to refrain from all alcohol consumption beginning 72 hours prior to first administration of study drug and throughout the study until the final study visit.
15. Subject consumes excessive amounts of caffeine for one month prior to study drug administration, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola or other caffeinated beverages per day.
16. Subject has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 30 days or 5 half-lives of the investigational product prior to the screening. The 30-day window will be derived from the date of the last study procedure (i.e., poststudy, AE follow-up, etc.) in the previous study to the screening visit of the current study.
17. Subject was vaccinated with a live vaccine within 4 weeks prior to the first administration of the study drug.
18. Subject has a history of significant multiple and/or severe allergies [including latex allergy, but with exception of seasonal rhinitis (hay fever)] or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
19. Subject is currently an abuser including illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year.
20. Subject tested positive for drugs of abuse, including amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, methadone and opiates at screening or Day -1.
21. There is any concern by the investigator regarding the safe participation of the subject in the study or for any other reason the investigator considers the subject inappropriate for participation in the study.
22. Subject is unable to abstain from strenuous exercise from 48 hours prior to Day - 1 throughout the study until the poststudy visit.

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/12/2024
Actual
Date of last participant enrolment
Anticipated
15/07/2025
Actual
Date of last data collection
Anticipated
29/08/2025
Actual
Sample size
Target
112
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27151 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 43231 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 317462 0
Commercial sector/Industry
Name [1] 317462 0
SCYNEXIS, Inc
Country [1] 317462 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
SCYNEXIS, Inc
Address
Country
United States of America
Secondary sponsor category [1] 319751 0
None
Name [1] 319751 0
Address [1] 319751 0
Country [1] 319751 0
Other collaborator category [1] 283241 0
Commercial sector/Industry
Name [1] 283241 0
Novotech(Australia) Pty Limited
Address [1] 283241 0
Country [1] 283241 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316177 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 316177 0
https://bellberry.com.au/
Ethics committee country [1] 316177 0
Australia
Date submitted for ethics approval [1] 316177 0
25/09/2024
Approval date [1] 316177 0
28/10/2024
Ethics approval number [1] 316177 0
2024-09-1242

Summary
Brief summary
A Four-Part, Phase 1, First-in-Human, Single and Multiple-Ascending Dose and Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Oral SCY-247 in Healthy Subjects.

The current study is the first clinical administration of SCY-247 to be conducted in healthy adult subjects. It is a 4-part study combining Part 1: single ascending dose (SAD), Part 2: multiple ascending dose (MAD), Part 3: loading and maintenance doses,
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137038 0
Dr Christopher Argent
Address 137038 0
Scientia Clinical Research Ltd, The Bright Building, Level 5, Corner High & Avoca Streets, Randwick NSW 2031
Country 137038 0
Australia
Phone 137038 0
+61 0458 639 115
Fax 137038 0
Email 137038 0
[email protected]
Contact person for public queries
Name 137039 0
Philip Deane
Address 137039 0
SCYNEXIS, Inc., 1 Evertrust Plaza, Jersey City, NJ 07302
Country 137039 0
United States of America
Phone 137039 0
+1 973 307 7997
Fax 137039 0
Email 137039 0
[email protected]
Contact person for scientific queries
Name 137040 0
Christopher Argent
Address 137040 0
Scientia Clinical Research Ltd,, The Bright Building, Level 5, Corner High & Avoca Streets, Randwick NSW 2031
Country 137040 0
Australia
Phone 137040 0
+61 2 9382 5800
Fax 137040 0
Email 137040 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.