Safety and Tolerability of CFTX-1554 in Healthy Subjects

Study Overview
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Brief Summary
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The study will consist of 2 parts, i.e. a single ascending dose part with integrated food effect assessment and assessment of relative bioavailability (Part A), and a multiple ascending dose part (Part B). Part A will have a randomized, double-blind, placebo-controlled design. Subjects will receive single ascending doses of CFTX-1554 or placebo (as liquid formulation under fasted condition) in 7 subsequent cohorts. Drug intake under fed conditions, and as capsule under fasted conditions and under fed conditions (Periods 2 to 4), compared to liquid formulation under fasted conditions (Period 1) (1 single dose level only) will be assessed. Part B will have a randomized, double-blind, placebo-controlled design, assessing multiple ascending oral doses of CFTX-1554 or placebo in 4 subsequent cohorts.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of CFTX-1554 in Healthy Subjects, With Comparison of Intake of CFTX-1554 as Liquid Formulation and as Capsule, and After a High-fat Breakfast Versus Fasted

Conditions
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Healthy

Intervention / Treatment
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* Drug: CFTX-1554
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Body mass index 18.0 to 30.0 kg/m2 Females may be of childbearing potential but not pregnant or lactating, or of nonchildbearing potential; all females will be required to have a negative serum pregnancy test conducted at screening, (each) admission, and follow-up. Female subjects of childbearing potential who have a fertile male sexual partner must agree to use adequate contraception from at least 4 weeks prior to first administration of study drug until 90 days after the follow up visit. Male subjects, if not surgically sterilized, must agree to use adequate contraception and not donate sperm from first admission to the clinical research center until 90 days after the follow-up visit. All prescribed medication must have been stopped at least 30 days prior to first admission to the clinical research center. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications must have been stopped at least 14 days prior to first admission to the clinical research center. Ability and willingness to abstain from alcohol from 48 hours before screening and first admission to the clinical research center. Ability and willingness to abstain from methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks) and grapefruit (juice) from 48 hours before first admission to the clinical research center. Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs, as judged by the Investigator. Willing and able to sign the Informed Consent Form. EXCLUSION CRITERIA: Previous participation in the current study History of relevant drug and/or food allergies Allergy or hypersensitivity to active ingredient or excipients of the study drug Using nicotine-containing products within 60 days prior to the first study drug administration History of alcohol abuse or drug addiction (including soft drugs like cannabis products) within 1 year before screening Positive drug and alcohol screen in urine (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, nicotine metabolites [cotinine], and alcohol) at screening or at one of the admissions to the clinical research center Average intake of >24 units of alcohol/week Positive screen for hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus 1 and 2 antibodies Participation in a drug study within 30 days prior to the first study drug administration in the current study (counting from the follow-up visit to the screening visit). Participation in ≥4 other drug studies in the 12 months before the first study drug administration in the current study Donation or loss of >450 mL of blood within 60 days pribefore the first study drug administration. Donation or loss of >1.5 L of blood in male subjects) or >1.0 L of blood in female subjects in the 10 months before the first study drug administration in the current study. Significant and/or acute illness within 5 days before the first study drug administration that may impact safety assessments, in the opinion of the Investigator. Unwillingness to consume the Food and Drug Administration (FDA) breakfast or intolerance to any of the ingredients of the FDA breakfast (Cohort A5 only) Vaccination against SARS-CoV-2 planned between 2 weeks before first admission and follow-up. Positive nasopharyngeal PCR test for SARS-CoV-2 on Day -1, or any known contact with a person who tested positive for SARS-CoV-2 or with a COVID 19 patient within 2 weeks before admission.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: CFTX-1554 Single Ascending Dose (SAD)<br>Up to 7 dose levels with CFTX-1554 administered as oral liquid formulation under fasted conditions (at 1 single dose level only, drug intake under fed conditions, and as capsule under fasted conditions and under fed conditions, will be assessed) | Drug: CFTX-1554<br>* CFTX-1554 is a new chemical entity that binds to the angiotensin II type 2 receptor (AT2R).<br>|
| Placebo Comparator: Part A placebo<br>Single placebo administration in study Part A | Drug: Placebo<br>* CFTX-1554 matching placebo<br>|
| Experimental: Part B: CFTX-1554 Multiple Ascending Dose (MAD)<br>Up to 4 dose levels with CFTX-1554 in Part B. Doses and dosing frequency will be decided based on the results of study Part A. | Drug: CFTX-1554<br>* CFTX-1554 is a new chemical entity that binds to the angiotensin II type 2 receptor (AT2R).<br>|
| Placebo Comparator: Part B placebo<br>Multiple placebo administration in study Part B | Drug: Placebo<br>* CFTX-1554 matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Number of Participants With Adverse Events Following Oral Administration of CFTX-1554 in SAD (Part A) and MAD (Part B) | Day -1 through Day 13 (Single Ascending Dose study part) or Day 26 (Multiple Ascending Dose study part) |