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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control (normal renal function or mild renal impairment) | Experimental | Estimated glomerular filtration rate (eGFR) ≥60 mL/min |
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| Moderate to severe renal impairment | Experimental | eGFR 15 to 59 mL/min |
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| Kidney failure | Experimental | eGFR <15 mL/min, including:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CIN-107 | Drug | A single 10 mg CIN-107 oral dose (2 X 5 mg tablets). |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration (Cmax) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit. | up to Day 8 |
| Time to maximum plasma concentration (Tmax) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit. | up to Day 8 |
| Area under the curve from time 0 to the time of last quantifiable plasma concentration (AUC[0-last]) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit. | up to Day 8 |
| Area under the curve from time 0 to infinity (AUC[0-inf]) | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit. | up to Day 8 |
| Percent of AUC extrapolated | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit. | up to Day 8 |
| Terminal phase elimination half-life | This PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites using plasma concentration data, as the data permit. |
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Inclusion Criteria:
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:
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;
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orlando Clinical Research Center | Orlando | Florida | 32809 | United States | ||
| Genesis Clinical Trials |
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| Label | URL |
|---|---|
| Redacted CSR Synopsis | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| up to Day 8 |
| Apparent plasma clearance (CL/F) | This PK parameter will be determined for CIN-107 using plasma concentration data. | up to Day 8 |
| Apparent volume of distribution | This PK parameter will be determined for CIN-107 using plasma concentration data. | up to Day 8 |
| The cumulative amount of CIN-107 and CIN-107-M excreted in the urine (Ae) | This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M) | up to Day 8 |
| Renal clearance (CLR) of CIN-107 and CIN-107-M of CIN-107 and CIN-107-M | Calculated as Ae/AUC. This PK parameter will be calculated using the urine concentrations of CIN-107 and its primary metabolite (CIN-107-M) | up to Day 8 |
| The fraction of the dose excreted renally | This PK parameter will be calculated using the urine concentrations of CIN-107 | up to Day 8 |
| Number of patients experiencing adverse events (AEs) | up to Day 11 |
| Number of patients experiencing adverse drug reactions | up to Day 11 |
| Number of patients experiencing serious adverse events (SAEs) | up to Day 11 |
| Tampa |
| Florida |
| 33603 |
| United States |