Clinical trial NCT05470725: Study to Evaluate the Pharmacokinetics of CIN-107 in Subjects With Varying Degrees of Renal Function
Official title: A Phase 1, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Pharmacokinetics of CIN-107 in Subjects With Varying Degrees of Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-07-22
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, open-label, parallel-group study in subjects with varying degrees of renal function to assess the safety, tolerability, and Pharmacokinetics of a single 10 mg oral dose of CIN-107.


Eligibility criteria: Inclusion Criteria:

* Subjects in stable health based on medical and psychiatric history, physical examination, ECG, vital signs (seated and orthostatic), and routine laboratory tests (chemistry, hematology, coagulation, and urinalysis); Note: Underlying medical conditions consistent with the population under study are acceptable if the subject's condition is considered stable by the Investigator. For renally impaired subjects, their renal status must be stable for a minimum of 3 months prior to screening.
* Does not use nicotine-containing products at all or smokes \<10 cigarettes/day (approximately \<half pack/day);
* Body mass index (BMI) between 18 and 40 kg/m2, inclusive;

Exclusion Criteria:

* Active participation in another experimental therapy study of a small molecule other than CIN-107 within 30 days prior to Day 1 or 5 half-lives, whichever is longer; or received a large molecule within 90 days prior to Day 1 or 5 half-lives, whichever is longer;
* History of prior organ transplant or planned transplant within 6 months of screening;
* Personal or family history of long QT syndrome, torsades de pointes, or other complex ventricular arrhythmias, or family history of sudden death;
* History of, or current, clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, chronic persistent atrial fibrillation, sinus node dysfunction, or clinically significant heart block. Subjects with minor forms of ectopy (eg, premature atrial contractions) are not necessarily excluded;
* Prolonged QTcF (\>450 msec for males or \>470 msec for females) based on the average of triplicate ECGs;
* Evidence of any of the following clinical measurements:

  1. Seated systolic BP \>160 mmHg and/or diastolic BP \>100 mmHg, or systolic BP \<90 mmHg and/or diastolic BP \<50 mmHg;
  2. Resting heart rate \>100 beats per minute (bpm) or \<50 bpm;
  3. Oral temperature \>37.6°C (\>99.68°F);
  4. Respiration rate 20 breaths/minute;
  5. Postural tachycardia (ie, an increase in heart rate \>30 bpm upon standing from a seated position);
  6. Orthostatic hypotension (ie, a fall in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg upon standing from a seated position);
  7. Clinically significant abnormal serum potassium \>upper limit of normal of the reference range (ULN);
  8. Clinically significant abnormal serum sodium 1.5 x ULN;
  9. Aspartate aminotransferase or alanine aminotransferase values \>1.5 x ULN
  10. Total bilirubin \>2 x ULN, unless due to Gilbert's syndrome;
  11. Positive test for HIV antibody, hepatitis C virus (HCV) RNA, hepatitis B surface antigen (HBsAg), or SARS-CoV-2 RNA; or
* History of porphyria, myopathy, or active liver disease;
* Inadequate venous access;
* Current treatment with weight loss medication or prior weight loss surgery (eg, gastric bypass surgery);
* Use of a strong inducer of CYP3A4 within 28 days prior to the dose of study drug;
* Corticosteroid use (systemic or extensive topical use) within 3 months prior to study drug dosing;
* Positive drug or alcohol test result without medical explanation or a history of alcoholism or drug abuse within 2 years prior to study drug dosing as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition;
* Typical consumption of ≥14 alcoholic drinks weekly;
* Surgical procedures within 4 weeks prior to study drug dosing or planned elective surgery during the study period;
* Any clinically significant illness within 4 weeks prior to study drug dosing, unless deemed not clinically significant by the Investigator;
* Pregnant, breastfeeding, or planning to become pregnant during the study;

Primary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: up to Day 8
measure: Time to maximum plasma concentration (Tmax)
timeFrame: up to Day 8
measure: Area under the curve from time 0 to the time of last quantifiable plasma concentration (AUC[0-last])
timeFrame: up to Day 8
measure: Area under the curve from time 0 to infinity (AUC[0-inf])
timeFrame: up to Day 8
measure: Percent of AUC extrapolated
timeFrame: up to Day 8
measure: Terminal phase elimination half-life
timeFrame: up to Day 8
measure: Apparent plasma clearance (CL/F)
timeFrame: up to Day 8
measure: Apparent volume of distribution
timeFrame: up to Day 8
measure: The cumulative amount of CIN-107 and CIN-107-M excreted in the urine (Ae)
timeFrame: up to Day 8
measure: Renal clearance (CLR) of CIN-107 and CIN-107-M of CIN-107 and CIN-107-M
timeFrame: up to Day 8
measure: The fraction of the dose excreted renally
timeFrame: up to Day 8
measure: Number of patients experiencing adverse events (AEs)
timeFrame: up to Day 11
measure: Number of patients experiencing adverse drug reactions
timeFrame: up to Day 11
measure: Number of patients experiencing serious adverse events (SAEs)
timeFrame: up to Day 11
Secondary outcomes:
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Tampa
country: United States
facility: Genesis Clinical Trials
state: Florida
Study officials:
References: