Study With CIN-107 Following Multiple Oral Ascending Doses in Healthy Subjects

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: CIN-107; Drug: Matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05500820

CIN-107-111

Details and patient eligibility

About

This is a randomized, double-blind, study to assess the safety, tolerability, PK, and PD of multiple oral doses of CIN-107 when administered to healthy adult subjects.

Enrollment: 56 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy subjects between the ages of 18 and 55 years, inclusive, in good health based on medical and psychiatric history, physical examination, ECG, orthostatic vital signs, and routine laboratory tests (blood chemistry, hematology, coagulation, and urinalysis).
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive.
3. Nonsmokers who have not used nicotine-containing products for at least 6 months prior to the Screening Visit.

Exclusion criteria

1. Actively participating in an experimental therapy study; received experimental therapy with a small molecule within 30 days of Day 1, or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of Day 1, or 5 half-lives, whichever is longer.
2. A personal or family history of long QT syndrome, Torsades de Pointes, or other complex ventricular arrhythmias, or family history of sudden death.
3. History of, or current, clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, or atrial fibrillation.
4. Prolonged QTcF (>450 msec) based on the average of triplicate ECGs.
5. Seated blood pressure higher than 150/90 mmHg or lower than 90/50 mmHg.
6. Resting heart rate higher than 100 bpm or lower than 50 bpm , sinus node dysfunction, or clinically significant heart block.
7. Temperature (T) greater than 37.6o C (99.68o F, measured orally), and respiration rate less than 12 and greater than 20 breaths/minute.
8. Postural tachycardia (ie >30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic blood pressure (SBP) of ≥20 mm Hg or DBP of ≥ 10 mm Hg when a person assumes a standing position).
9. Serum potassium > upper limit of normal of the reference range (ULN) and serum sodium < lower limit of normal of the reference range (LLN).
10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values > 1.2 ULN.
11. Positive for human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody, or Hepatitis B surface antigen (HBsAg).
12. A known history of porphyria, myopathy, or an active liver disease.
13. Positive drug or alcohol test result or a history of alcoholism or drug abuse within 2 years prior to the first dose of study drug as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition: DSM-IV.
14. Typical consumption of ≥14 alcoholic drinks weekly.
15. Surgical procedures within 4 weeks of check-in or planned elective surgery during the study period.
16. Currently undergoing treatment with weight loss medication or prior weight loss surgery (eg, gastric bypass surgery).
17. Pregnant, breastfeeding, or planning to become pregnant during the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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56 participants in 10 patient groups, including a placebo group

Cohort 1: 2.5 mg CIN-107

Experimental group

Description:

Subjects on a low salt diet

Treatment:

Drug: CIN-107

Cohort 2: 5.0 mg CIN-107

Experimental group

Description:

Subjects on a low salt diet

Treatment:

Drug: CIN-107

Cohort 3: 1.5 mg CIN-107

Experimental group

Description:

Subjects on a normal salt diet

Treatment:

Drug: CIN-107

Cohort 4: 2.5 mg CIN-107

Experimental group

Description:

Subjects on a normal salt diet

Treatment:

Drug: CIN-107

Cohort 5: 0.5 mg CIN-107

Experimental group

Description:

Subjects on a normal salt diet

Treatment:

Drug: CIN-107

Cohort 1: 2.5 mg matching placebo

Placebo Comparator group

Description:

Subjects on a low salt diet

Treatment:

Drug: Matching Placebo

Cohort 2: 5.0 mg matching placebo

Placebo Comparator group

Description:

Subjects on a low salt diet

Treatment:

Drug: Matching Placebo

Cohort 3: 1.5 mg matching placebo

Placebo Comparator group

Description:

Subjects on a normal salt diet

Treatment:

Drug: Matching Placebo

Cohort 4: 2.5 mg matching placebo

Placebo Comparator group

Description:

Subjects on a normal salt diet

Treatment:

Drug: Matching Placebo

Cohort 5: 0.5 mg matching placebo

Placebo Comparator group

Description:

Subjects on a normal salt diet

Treatment:

Drug: Matching Placebo