HypertensionPhase 1NCT05526690
Study to Evaluate the Effect of CIN-107 on the Pharmacokinetics of the MATE Substrate, Metformin, in Healthy Subjects
A Phase 1 study testing Metformin and CIN-107 in people with Hypertension, run by AstraZeneca at 1 site in United States.
Trial summary
This is a randomized, open-label, two-period, crossover Phase 1 to assess the impact of CIN-107 on the pharmacokinetics (PK) of metformin and the safety and tolerability of coadministration of CIN-107 and metformin as compared to metformin alone. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- Metformin and CIN-107
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2020to 12 Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects between the ages of 18 and 55 years, inclusive, at Screening;
- Body mass index between 18 and 30 kg/m2, inclusive;
- In good health based on medical/surgical and psychiatric history, physical examination, electrocardiogram (ECG), vital signs (seated and orthostatic), and routine laboratory tests (serum chemistry, hematology, and urinalysis);
- Normal renal function, defined as estimated glomerular filtration rate ≥85 mL/min/1.73 m2 at Screening and Day -1;
- Nonsmokers who have not used nicotine-containing products (ie, cigarettes, nicotine patch, nicotine chewing gum, or electronic cigarettes) for at least 6 months prior to Screening;
Who cannot join
- Actively participating in an experimental therapy study; received experimental therapy with a small molecule other than CIN-107 within 30 days of the first dose of study drug or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of the first dose of study drug or 5 half-lives, whichever is longer;
- A personal or family history of long QT syndrome, Torsades de Pointes, 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, atrial fibrillation, sinus node dysfunction, or clinically significant heart block. Subjects with minor forms of ectopy (eg, premature atrial contractions) are not necessarily excluded and may be discussed with the Medical Monitor for inclusion;
- Prolonged QT interval corrected by Fridericia's formula (>450 msec);
- Seated systolic blood pressure (BP) >140 mmHg and/or diastolic BP >90 mmHg or systolic BP <90 mmHg and/or diastolic BP <50 mmHg;
- Postural tachycardia (ie, >30 bpm upon standing) or orthostatic hypotension (ie, a fall in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg upon standing);
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- Serum potassium >upper limit of normal (ULN) of the reference range and serum sodium <lower limit of normal of the reference range;
- Aspartate aminotransferase, alanine aminotransferase, or total bilirubin values >1.2 × ULN;
- Positive for human immunodeficiency virus antibody, hepatitis C virus antibody, hepatitis B surface antigen, or severe acute respiratory syndrome coronavirus 2 RNA;
- Evidence or history of any clinically significant immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, musculoskeletal, hepatic, psychiatric, neurologic, or allergic (including clinically significant or multiple drug allergies) disease; surgical conditions; cancer (with the exception of basal or squamous cell carcinoma of the skin and cancer that has resolved or has been in remission for >5 years prior to Screening); or any condition that, in the Investigator's opinion, may confound study procedures or results, impact subject safety, or interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendectomy allowed, cholecystectomy prohibited);
- Typical consumption of ≥14 alcoholic drinks weekly; Note: 1 drink of alcohol is equivalent to ½ pint of beer (285 mL), 1 glass of spirits (25 mL), or 1 glass of wine (125 mL).
- Surgical procedures within 4 weeks prior to Check-In (other than minor cosmetic surgery or minor dental procedures) or planned elective surgery during the treatment period;
Trial locations and contacts
1 site in 1 country.
United States1 site
Medpace Clinical Pharmacology Unit
Cincinnati, Ohio, 45227
About this study
Official title: A Randomized, Open-Label, Two-Period, Crossover Study to Evaluate the Effect of CIN-107 on the Pharmacokinetics of the MATE Substrate, Metformin, in Healthy Subjects
This is a randomized, open-label, two-period, crossover Phase 1 to assess the impact of CIN-107 on the pharmacokinetics (PK) of metformin and the safety and tolerability of coadministration of CIN-107 and metformin as compared to metformin alone.
- Conditions
- Hypertension
- Being tested
- Metformin, CIN-107
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
1000 mg dose of immediate-release metformin
CIN-107Drug
10 mg dose of CIN-107
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: Immediate-release metformin | Active comparator | Treatment A: single 1000 mg dose of immediate-release metformin
Subjects will be randomly assigned to 1 of 2 sequences: AB or BA.
* Treatment A: a single 1000 mg dose of immediate-release metformin; and
* Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107.
All study medication will be administered at 8:00 AM (±2 hours). There will be a minimum 10-day washout between administration of study drug in each treatment period. Receives: Drug: Metformin |
| Treatment B: Immediate-release metformin coadministered with a CIN-107 | Experimental | Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107
Subjects will be randomly assigned to 1 of 2 sequences: AB or BA.
* Treatment A: a single 1000 mg dose of immediate-release metformin; and
* Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107.
All study medication will be administered at 8:00 AM (±2 hours). For Treatment B, the dose of CIN-107 will be administered 2 hours prior to the dose of metformin.
There will be a minimum 10-day washout between administration of study drug in each treatment period. Receives: Drug: Metformin; Drug: CIN-107 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma concentration (Cmax)
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Measured: Up to day 3
Time to Cmax (Tmax)
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Measured: Up to day 3
Area under the concentration-time curve (AUC) from time 0 to 72 hours
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Measured: Up to day 3
Maximum plasma concentration (Cmax) of metformin
This plasma PK parameter will be determined for metformin.
Measured: Up to day 3
Time to Cmax (Tmax) of metformin
This plasma PK parameter will be determined for metformin.
Measured: Up to day 3
AUC from time 0 to the time of last quantifiable plasma concentration of metformin
This plasma PK parameter will be determined for metformin.
Measured: Up to day 3
AUC from time 0 to infinity of metformin
This plasma PK parameter will be determined for metformin.
Measured: Up to day 3
Percent of AUC extrapolated of metformin
This plasma PK parameter will be determined for metformin.
Measured: Up to day 3
Terminal phase elimination half-life of metformin
This plasma PK parameter will be determined for metformin.
Measured: Up to day 3
Cumulative amount of metformin excreted in the urine (Ae) of metformin
This urine PK parameter will be determined for metformin.
Measured: Up to day 3
Renal clearance (calculated as Ae/AUC) of metformin
This urine PK parameter will be determined for metformin.
Measured: Up to day 3
Fraction of the dose excreted renally of metformin
This urine PK parameter will be determined for metformin.
Measured: Up to day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2022
- Study start28 Oct 2020
- Primary completion12 Dec 2020
- Study completion12 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Leela Leela Vrishabhendra, MD, MD, Principal investigator, Medpace Clinical Pharmacology Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05526690
- Sponsor's protocol ID
- CIN-107-114
- Status last verified
- Aug 2023
- First submitted
- 31 Aug 2022
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Freeman MW, Bond M, Murphy B, Hui J, Isaacsohn J. Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects. Am J Cardiovasc Drugs. 2023 May;23(3):277-286. doi: 10.1007/s40256-023-00572-x. Epub 2023 Feb 15.
PubMed 36790596
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Two-Period, Crossover Study to Evaluate the Effect of CIN-107 on the Pharmacokinetics of the MATE Substrate, Metformin, in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05526690
- Acronym / sponsor ID
- CIN-107-114
- Conditions
- Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 12 Dec 2020 (actual)
- Study completion
- 12 Dec 2020 (actual)
- First posted
- 2 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, open-label, two-period, crossover Phase 1 to assess the impact of CIN-107 on the pharmacokinetics (PK) of metformin and the safety and tolerability of coadministration of CIN-107 and metformin as compared to metformin alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A: Immediate-release metformin | Active comparator | Drug: MetforminTreatment A: single 1000 mg dose of immediate-release metformin Subjects will be randomly assigned to 1 of 2 sequences: AB or BA. * Treatment A: a single 1000 mg dose of immediate-release metformin; and * Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107. All study medication will be administered at 8:00 AM (±2 hours). There will be a minimum 10-day washout between administration of study drug in each treatment period. |
| Treatment B: Immediate-release metformin coadministered with a CIN-107 | Experimental | Drug: Metformin, Drug: CIN-107Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107 Subjects will be randomly assigned to 1 of 2 sequences: AB or BA. * Treatment A: a single 1000 mg dose of immediate-release metformin; and * Treatment B: a single 1000 mg dose of immediate-release metformin coadministered with a 10 mg dose of CIN-107. All study medication will be administered at 8:00 AM (±2 hours). For Treatment B, the dose of CIN-107 will be administered 2 hours prior to the dose of metformin. There will be a minimum 10-day washout between administration of study drug in each treatment period. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy subjects between the ages of 18 and 55 years, inclusive, at Screening;
- Body mass index between 18 and 30 kg/m2, inclusive;
- In good health based on medical/surgical and psychiatric history, physical examination, electrocardiogram (ECG), vital signs (seated and orthostatic), and routine laboratory tests (serum chemistry, hematology, and urinalysis);
- Normal renal function, defined as estimated glomerular filtration rate ≥85 mL/min/1.73 m2 at Screening and Day -1;
- Nonsmokers who have not used nicotine-containing products (ie, cigarettes, nicotine patch, nicotine chewing gum, or electronic cigarettes) for at least 6 months prior to Screening;
Key exclusion criteria (12 listed)
- Actively participating in an experimental therapy study; received experimental therapy with a small molecule other than CIN-107 within 30 days of the first dose of study drug or 5 half-lives, whichever is longer; or received experimental therapy with a large molecule within 90 days of the first dose of study drug or 5 half-lives, whichever is longer;
- A personal or family history of long QT syndrome, Torsades de Pointes, 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, atrial fibrillation, sinus node dysfunction, or clinically significant heart block. Subjects with minor forms of ectopy (eg, premature atrial contractions) are not necessarily excluded and may be discussed with the Medical Monitor for inclusion;
- Prolonged QT interval corrected by Fridericia's formula (>450 msec);
- Seated systolic blood pressure (BP) >140 mmHg and/or diastolic BP >90 mmHg or systolic BP <90 mmHg and/or diastolic BP <50 mmHg;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin1000 mg dose of immediate-release metformin | Drug | Treatment A: Immediate-release metformin, Treatment B: Immediate-release metformin coadministered with a CIN-107 |
| CIN-10710 mg dose of CIN-107 | Drug | Treatment B: Immediate-release metformin coadministered with a CIN-107 |
Primary outcome
Maximum plasma concentration (Cmax)
Time frame: Up to day 3
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Time to Cmax (Tmax)
Time frame: Up to day 3
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Area under the concentration-time curve (AUC) from time 0 to 72 hours
Time frame: Up to day 3
This plasma PK parameter will be determined for CIN-107, its primary metabolite (CIN-107-M), and any other measured metabolites.
Maximum plasma concentration (Cmax) of metformin
Time frame: Up to day 3
This plasma PK parameter will be determined for metformin.
Time to Cmax (Tmax) of metformin
Time frame: Up to day 3
This plasma PK parameter will be determined for metformin.
AUC from time 0 to the time of last quantifiable plasma concentration of metformin
Time frame: Up to day 3
This plasma PK parameter will be determined for metformin.
AUC from time 0 to infinity of metformin
Time frame: Up to day 3
This plasma PK parameter will be determined for metformin.
Percent of AUC extrapolated of metformin
Time frame: Up to day 3
This plasma PK parameter will be determined for metformin.
Terminal phase elimination half-life of metformin
Time frame: Up to day 3
This plasma PK parameter will be determined for metformin.
Cumulative amount of metformin excreted in the urine (Ae) of metformin
Time frame: Up to day 3
This urine PK parameter will be determined for metformin.
Renal clearance (calculated as Ae/AUC) of metformin
Time frame: Up to day 3
This urine PK parameter will be determined for metformin.
Fraction of the dose excreted renally of metformin
Time frame: Up to day 3
This urine PK parameter will be determined for metformin.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
- Background: PubMed 36790596Freeman MW, Bond M, Murphy B, Hui J, Isaacsohn J. Results From a Randomized, Open-Label, Crossover Study Evaluating the Effect of the Aldosterone Synthase Inhibitor Baxdrostat on the Pharmacokinetics of Metformin in Healthy Human Subjects. Am J Cardiovasc Drugs. 2023 May;23(3):277-286. doi: 10.1007/s40256-023-00572-x. Epub 2023 Feb 15.
- Redacted CSR SynopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leela Leela Vrishabhendra, MD, MD principal investigator
Medpace Clinical Pharmacology Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin and CIN-107 in people with Hypertension, run by AstraZeneca at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum plasma concentration (Cmax) (time frame: Up to day 3). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05526690, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2023.