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Trial registered on ANZCTR


Registration number
ACTRN12624001393549
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 4
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 4
Secondary ID [1] 313071 0
SCY-247-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fungal Infection 335307 0
Condition category
Condition code
Infection 331879 331879 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. This registration is for Part 4.

Part 4 – Drug-Drug Interaction: This is an open-label, drug-drug interaction evaluation in 2 Cohorts of 12 subjects each. Part 4 Cohort 1 will evaluate the effect of a proton pump inhibitor (pantoprazole) on single-dose PK of SCY-247 and Part 4 Cohort 2 will evaluate the effect of a strong CYP3A4 inhibitor (posaconazole) on single-dose PK of SCY-247. All SCY-247 doses will be administered in the fasted state (no solid food for 8 hours). The interval between successive doses of SCY-247 will be at least 7 days.

Part 4, 2 Cohorts:
Cohort 1, Period 1: Single Dose administration of SCY-247 400-mg on Day 1
Cohort 1, Period 2: Pantoprazole 40-mg oral tablet once daily Days -4 to Day 1; SCY-247 400- mg on Day 1, 2.5 hours after pantoprazole dose
Cohort 2, Period 1: Single Dose administration of SCY-247 200-mg on Day 1
Cohort 2, Period 2: Posaconazole 300-mg DR tablets twice daily on Day -1 and once daily from Day 1 through Day 10; SCY-247 200-mg on Day 1, co-administered with posaconazole

Administration of SCY-247 is planned to be in the fasted state but may be changed to administration in fed state (no fasting prior to dosing) if 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.
Intervention code [1] 329627 0
Treatment: Drugs
Comparator / control treatment
Cohort 1- Participants will receive only Pantoprazole 40 mg (Apotex pantoprazole-as sodium sesquihydrate) tablet on period 2 only. Dosing details- Once daily from Day -4 to Day -1. On Day 1 the participants will receive Pantoprazole 40 mg tablet along with SCY-247.

Cohort 2- Participants will receive only Posaconazole 300mg DR tablets as comparator on period 2 only. Dosing details- Twice daily on Day -1 and once daily from Day 2 through Day 10. On Day 1 the participants will receive Posaconazole 300mg DR tablet along with SCY-247.
Control group
Active

Outcomes
Primary outcome [1] 339496 0
To assess the effect of multiple doses of pantoprazole, a strong proton pump inhibitor, on the single-dose PK profile of SCY-247.
Timepoint [1] 339496 0
Blood samples will be collected on Day 1 predose and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours after SCY247 dose administration for Cohort 1;

Primary outcome [2] 339497 0
To assess the effect of multiple doses of posaconazole, a strong CYP3A4 inhibitor, on the single-dose PK profile of SCY-247
Timepoint [2] 339497 0
Blood samples were collected on Day 1 predose and at 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours after SCY-247 dose administration for Cohort 2 period 1 and additionally at 144, 168, 192, 216, 240 and 264 hours after SCY-247 dose administration for period 2.
Secondary outcome [1] 440192 0
To evaluate the safety and tolerability of coadministration of oral SCY-247 with pantoprazole in healthy subjects. All assessments will be measured as composite outcome.
Timepoint [1] 440192 0
- Adverse events monitored from screening to end of study (EOS) Day 14 for post first dose administration.
- Safety Lab parameters from screening to end of study (EOS) Day 14 for post first dose administration.
- Vital signs will be assessed from screening to end of study (EOS) Day 14 for post first dose administration.
Secondary outcome [2] 440193 0
To evaluate the safety and tolerability of coadministration of oral SCY-247 with posaconazole in healthy subjects. All assessments will be measured as composite outcome.
Timepoint [2] 440193 0
- Adverse events monitored from screening to end of study (EOS) Day 24 for post first dose administration.
- Safety Lab parameters from screening to end of study (EOS) Day 24 for post first dose administration.
- Vital signs will be assessed from screening to end of study (EOS) Day 24 for post first dose administration.

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. 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 equals 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 equals 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
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
As the participants undergo both the intervention and control treatments the intervention assignment has been marked as other.
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
15/08/2025
Actual
Date of last data collection
Anticipated
29/08/2025
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27153 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 43233 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 317512 0
Commercial sector/Industry
Name [1] 317512 0
SCYNEXIS, Inc
Country [1] 317512 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
SCYNEXIS, Inc
Address
Country
United States of America
Secondary sponsor category [1] 319811 0
None
Name [1] 319811 0
Address [1] 319811 0
Country [1] 319811 0
Other collaborator category [1] 283242 0
Commercial sector/Industry
Name [1] 283242 0
Novotech(Australia) Pty Limited
Address [1] 283242 0
Country [1] 283242 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316224 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 316224 0
https://bellberry.com.au/
Ethics committee country [1] 316224 0
Australia
Date submitted for ethics approval [1] 316224 0
25/09/2024
Approval date [1] 316224 0
28/10/2024
Ethics approval number [1] 316224 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 where Part 4 will evaluate drug-drug interaction where 24 subjects will be enrolled across 2 cohorts. The study duration from screening to post study visit will be approximately 9 weeks for Part 4.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137206 0
Dr Christopher Argent
Address 137206 0
Scientia Clinical Research Ltd, The Bright Building, Level 5, Corner High & Avoca Streets, Randwick NSW 2031
Country 137206 0
Australia
Phone 137206 0
+61 0458 639 115
Fax 137206 0
Email 137206 0
[email protected]
Contact person for public queries
Name 137207 0
Philip Deane
Address 137207 0
SCYNEXIS, Inc., 1 Evertrust Plaza, Jersey City, NJ 07302
Country 137207 0
United States of America
Phone 137207 0
+1 973 307 7997
Fax 137207 0
Email 137207 0
[email protected]
Contact person for scientific queries
Name 137208 0
Christopher Argent
Address 137208 0
Scientia Clinical Research Ltd, The Bright Building, Level 5, Corner High & Avoca Streets, Randwick NSW 2031
Country 137208 0
Australia
Phone 137208 0
+61 2 9382 5800
Fax 137208 0
Email 137208 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.