A Study of CIN-107 in Adults With Primary Aldosteronism

Overview

About this study

The purpose of this study is to evaluate the change from  baseline  in systolic blood pressure (SBP) by automated office blood  pressure monitoring  (AOBPM), with each dose  of CIN-107 compared to placebo, after 4 weeks of treatment in patients with PA.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Is an adult male or female patient greater than or equal to 18 years of age.
  • Has a prior diagnosis of PA or suspected diagnosis of PA per the Investigator’s judgement.
  • Is able to wash out of RAAS-modifying drug(s) at Visit 2, for the following durations before Visit 3:
    • ≥ 4 weeks: diuretics, including MRAs;
    • ≥ 2 weeks: beta blockers, clonidine, methyldopa, minoxidil, NSAIDs, ACEIs, ARBs, and/or dihydropyridine CCBs.
    • Note: Patients will remain off all RAAS-modifying drug(s) beginning at Visit 2 and through the End of Treatment. Patients may be placed on non-RAAS-modifying antihypertensive drug(s), defined as mono- or combination therapy with a non-dihydropyridine CCB (e.g., diltiazem, verapamil), hydralazine, or an alpha blocker, irrespective of their washout status, so  as  to  maintain  BP >130/80  mmHg  and  < 160/100  mmHg  for  the  remainder  of  the Screening Period and to minimize the effect on PAC and PRA. Patients taking beta-blockers should be managed appropriately by the Investigator during washout which should include gradual  down-titration  and  observation  of these  patients  for  withdrawal  symptoms (e.g., palpitations, chest pain, etc).
  • Is willing to have BP maintained > 130/80 mmHg and < 160/100 mmHg during the Screening Period and  < 160/100  mmHg  during  the  Double-Blind  Treatment  Period  with  the  use  of allowable non-RAAS-modifying antihypertensive drug(s).
  • Is willing to be compliant with the contraception and reproduction restrictions of the study as follows:
    • Postmenopausal women must have not had menstrual bleeding for at least 1 year before initial dosing  and  either  be  > 60  years  or  have  an  elevated  follicle-stimulating  hormone (FSH) level > 40 mIU/mL at the Screening Visit;
    • Female patients of childbearing potential (FPCBPs) (i.e., ovulating, pre-menopausal, and not surgically sterile) must have a documented negative pregnancy test at the Screening and Randomization Visits;
    • FPCBPs and all male patients (unless surgically sterile) must use a highly effective method of contraception (i.e., <1% failure rate) during their participation in the study and for up to 30 days after the last administration of study drug; Acceptable methods of contraception for male patients enrolled in the study include the following:
      • Condoms with spermicide;
      • Surgical sterilization (vasectomy) at least 26 weeks before the Screening Visit; Acceptable methods of contraception for FPCBP enrolled in the study include the following:o Intrauterine device for at least 12 weeks before the Screening Visit;
      • Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before the Screening Visit; or o Diaphragm used in combination with spermicide.
  • Is able and willing to give informed consent for participation in the study.

Exclusion Criteria:

  • Has  a  single  occurrence  of  mean  seated  SBP  > 180  mmHg  or  DBP  >110  mmHg  or  has 2 consecutive occurrences of mean seated SBP ≥ 160 mmHg or DBP ≥1 00 mmHg by AOBPM during the Screening Period (If such a BP is recorded at Visit 1, the patient will attend an Interim  Visit  for  the second  BP  measurement  and  reassessment  of  Inclusion/Exclusion Criteria).
    • Note: Mean seated BP is defined as the average of 3 measurements obtained at any 1 clinical site visit. If the patient missed the regularly scheduled antihypertensive medication(s) prior to the visit (Visits 1, 2, 3, or 4), and in the opinion of the Investigator has been otherwise adherent to their antihypertensive regimen, 1 BP re-test is allowed ≥ 2 hours after taking medication(s), or on the following day, or later after reestablishing the regularly scheduled antihypertensive regimen.
  • Has a body mass index (BMI) > 40 kg/m² at the Screening Visit.
  • Has an upper arm circumference < 7 or > 17 inches at the Screening Visit.
  • Has had a previous surgical intervention or has a planned surgical intervention for an adrenal adenoma or adrenal carcinoma, adrenalectomy, renal nerve denervation or adrenal ablative procedure during the course of the study.
    • Note:  Patients  who  have  had  a  procedure  >6  months  prior  to  randomization  but  still have elevated PAC (≥15 ng/dl) and meet BP and other eligibly criteria may be considered.
  • Has a documented estimated glomerular filtration rate <60 mL/min/1.73m² using the Chronic Kidney Disease Epidemiology equation at the Screening Visit or at Visit 4.
  • Has a planned dialysis or kidney transplantation during the course of the study.
  • Has known documented chronic heart failure.
  • Has  had  a  stroke, transient  ischemic attack, hypertensive  encephalopathy, acute coronary syndrome, or hospitalization for heart failure within 6 months before the Screening Visit.
  • Has known current severe left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease, diagnosed from a prior echocardiogram.
  • Has a planned  coronary  revascularization  (percutaneous  coronary  intervention  [PCI]  or coronary artery bypass graft [CABG]) or any major surgical procedure during the study.
  • Has had PCI, CABG, other major cardiac surgery (e.g., valve replacement), or peripheral arterial bypass surgery within 6 months before the Screening Visit.
  • Has chronic permanent atrial fibrillation.
  • Has a history of, or currently experiencing, clinically significant arrhythmias as judged by the Investigator, including ventricular tachycardia, ventricular fibrillation, Torsades de points, and supraventricular  arrhythmias.  Patients with minor  forms  of  ectopy (e.g., premature atrial contractions) are not necessarily excluded, per Investigator discretion.
  • Has had a prior solid organ transplant or cell transplant.
  • Is expected to receive or is receiving any of the exclusionary drugs such as strong inducers of cytochrome P450 3A, substrates for multidrug and toxin extrusion (MATE)1 and MATE2K, drugs known to prolong QT, chronic use of NSAIDs or steroids within 28 days or 5 half-lives, whichever is longer prior to the first dose of study drug until the end of treatment.
    • Note: patients who are using medication(s) noted above at Screening who are willing to come off during the course of the study are allowed to participate.
  • Is expected to receive or is receiving metformin within 28 days of the first dose of study drug until the end of treatment.
    • Note: patients who are using metformin at Screening who are willing to come off during the course of the study are allowed to participate.
  • Has a known hypersensitivity to any of the following:
    • CIN-107 or drugs of the same class;
    • Captopril or drugs of the same class;
    • Excipients in CIN-107, captopril, or drugs of the same classes.
  • Has any clinically relevant medical or surgical conditions (including unstable conditions and/or conditions requiring treatment with systemic immunosuppressants, including corticosteroids) that, in the opinion of the Investigator, would put the patient at risk by participating in the study.
  • Has evidence of any of the following at the Screening, Visit 4, or the Randomization Visit:
    • White blood cell count > 15 x 10⁹/L or absolute neutrophil count < 1 x 10⁹/L;
    • Serum potassium < 2.5 mEq/L;
    • Patients with a serum potassium level below normal range may continue in the study if the Investigator elects to correct the serum potassium level with supplementation and offers to manage the condition;
    • Serum potassium > 5.0 mEq/L;
    • Hemoglobin  < 10.0  g/dL or anticipated  initiation  of  erythropoietin-stimulating  agents or planned transfusion within 2 months after the Screening Visit;
    • Serum aspartate aminotransferase or alanine aminotransferase > 3  upper limit of normal (ULN);
    • Total bilirubin >2 ULN, unless due to Gilbert’s syndrome.
  • Has uncontrolled diabetes with glycosylated hemoglobin > 9.5% at the Screening Visit.
  • Is positive for HIV antibody, hepatitis C virus (HCV) RNA, or hepatitis B surface antigen (HBsAg).
  • Has 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).
  • Has participated in another clinical study involving any investigational drug within 30 days prior to the Screening Visit, or plans to participate in another clinical study within 30 days of discontinuation of study drug.
  • Has received experimental therapy with a small molecule within 30 days of the Screening Visit or 5 half-lives, whichever is longer, or received experimental therapy with a large molecule within 90 days of the Screening Visit or 5 half-lives, whichever is longer.
  • Has been on night shifts at any time during the 4 weeks before the Screening Visit and/or plans to begin night shift at any time during the Screening and/or Double-Blind Treatment period.
  • Is pregnant, breastfeeding, or planning to become pregnant during the study.
  • Is considered by the Investigator, after reviewing medical and psychiatric history, physical examination, and laboratory evaluations, to be unsuitable for any other reason that may either place the patient at increased risk during participation or interfere with the interpretation of the study outcomes.

Eligibility last updated 8/26/21. Questions regarding updates should be directed to the study team contact.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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12. Has chronic permanent atrial fibrillation;
13. Has a history of, or currently experiencing, clinically significant arrhythmias as judged by
the Investigator, including ventricular tachycardia, ventricular fibrillation, Torsades de points,
and supraventricular  arrhythmias.  Patients  with  minor  forms  of  ectopy  (eg,  premature 
atrial contractions) are not necessarily excluded, per Investigator discretion;
14. Has had a prior solid organ transplant or cell transplant;
15. Is expected to receive or is receiving any of the exclusionary drugs such as strong inducers of
cytochrome P450 3A, substrates for multidrug and toxin extrusion (MATE)1 and MATE2K, drugs known to
prolong QT, chronic use of NSAIDs or steroids within 28 days or 5 half-lives, whichever is longer
prior to the first dose of study drug until the end of treatment (see Section 5.6.1);
Note: patients who are using medication(s) noted above at Screening who are willing to come off
during the course of the study are allowed to participate.
16. Is expected to receive or is receiving metformin within 28 days of the first dose of study drug
until the end of treatment;
Note: patients who are using metformin at Screening who are willing to come off during the course
of the study are allowed to participate.
17. Has a known hypersensitivity to any of the following:
•    CIN-107 or drugs of the same class;
•    Captopril or drugs of the same class; or
•    Excipients in CIN-107, captopril, or drugs of the same classes;
18. Has any clinically relevant medical or surgical conditions (including unstable conditions
and/or conditions requiring treatment with systemic immunosuppressants, including corticosteroids)
that, in the opinion of the Investigator, would put the patient at risk by participating in the
study;
19. Has evidence of any of the following at the Screening, Visit 4, or the Randomization Visit:
•    White blood cell count >15  10⁹/L or absolute neutrophil count <1  10⁹/L;
•    Serum potassium <2.5 mEq/L;
Note: Patients with a serum potassium level below normal range may continue in the study if the
Investigator elects to correct the serum potassium level with supplementation and offers to manage
the condition.
•    Serum potassium >5.0 mEq/L;
•    Hemoglobin  <10.0  g/dL  or  anticipated  initiation  of  erythropoietin-stimulating  agents 
or planned transfusion within 2 months after the Screening Visit;
•    Serum aspartate aminotransferase or alanine aminotransferase >3  upper limit of normal (ULN);
or
•    Total bilirubin >2  ULN, unless due to Gilbert’s syndrome;

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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20. Has uncontrolled diabetes with glycosylated hemoglobin >9.5% at the Screening Visit;
21. Is positive for HIV antibody, hepatitis C virus (HCV) RNA, or hepatitis B surface antigen
(HBsAg);
22. Has 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).
23. Has participated in another clinical study involving any investigational drug within 30 days
prior to the Screening Visit, or plans to participate in another clinical study within 30 days of
discontinuation of study drug;
24. Has received experimental therapy with a small molecule within 30 days of the Screening Visit
or 5 half-lives, whichever is longer, or received experimental therapy with a large molecule within
90 days of the Screening Visit or 5 half-lives, whichever is longer;
25. Has been on night shifts at any time during the 4 weeks before the Screening Visit and/or plans
to begin night shift at any time during the Screening and/or Double-Blind Treatment period;
26. Is pregnant, breastfeeding, or planning to become pregnant during the study; or
27. Is considered by the Investigator, after reviewing medical and psychiatric history, physical
examination, and laboratory evaluations, to be unsuitable for any other reason that may either
place the patient at increased risk during participation or interfere with the interpretation of
the
study outcomes.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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7.   Has known documented chronic heart failure;
8.   Has  had  a  stroke,  transient  ischemic  attack,  hypertensive  encephalopathy,  acute 
coronary syndrome, or hospitalization for heart failure within 6 months before the Screening Visit;
9.   Has   known   current   severe   left   ventricular   outflow   obstruction,   such   as  
obstructive hypertrophic cardiomyopathy and/or severe aortic valvular disease, diagnosed from a
prior echocardiogram;
10. Has  a  planned  coronary  revascularization  (percutaneous  coronary  intervention  [PCI]  or
coronary artery bypass graft [CABG]) or any major surgical procedure during the study;
11. Has  had  PCI,  CABG,  other  major  cardiac  surgery  (eg,  valve  replacement),  or 
peripheral arterial bypass surgery within 6 months before the Screening Visit;
12. Has chronic permanent atrial fibrillation;
13. Has a history of, or currently experiencing, clinically significant arrhythmias as judged by
the Investigator, including ventricular tachycardia, ventricular fibrillation, Torsades de points,
and supraventricular  arrhythmias.  Patients  with  minor  forms  of  ectopy  (eg,  premature 
atrial contractions) are not necessarily excluded, per Investigator discretion;
14. Has had a prior solid organ transplant or cell transplant;
15. Is expected to receive or is receiving any of the exclusionary drugs such as strong inducers of
cytochrome P450 3A, substrates for multidrug and toxin extrusion (MATE)1 and MATE2K, drugs known to
prolong QT, chronic use of NSAIDs or steroids within 28 days or 5 half-lives, whichever is longer
prior to the first dose of study drug until the end of treatment;
Note: patients who are using medication(s) noted above at Screening who are willing to come off
during the course of the study are allowed to participate.
16. Is expected to receive or is receiving metformin within 28 days of the first dose of study drug
until the end of treatment;
Note: patients who are using metformin at Screening who are willing to come off during the course
of the study are allowed to participate.
17. Has a known hypersensitivity to any of the following:
•    CIN-107 or drugs of the same class;
•    Captopril or drugs of the same class; or
•    Excipients in CIN-107, captopril, or drugs of the same classes;
18. Has  any  clinically  relevant  medical  or  surgical  conditions  (including  unstable 
conditions and/or   conditions   requiring   treatment   with   systemic   immunosuppressants,  
including corticosteroids)  that,  in  the  opinion  of  the  Investigator,  would  put  the 
patient  at  risk  by participating in the study;

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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19. Has evidence of any of the following at the Screening, Visit 4, or the Randomization Visit:
•    White blood cell count >15  10⁹/L or absolute neutrophil count <1  10⁹/L;
•    Serum potassium <2.5 mEq/L;
Note: Patients with a serum potassium level below normal range may continue in the study if the
Investigator elects to correct the serum potassium level with supplementation and offers to manage
the condition.
•    Serum potassium >5.0 mEq/L;
•    Hemoglobin  <10.0  g/dL  or  anticipated  initiation  of  erythropoietin-stimulating  agents 
or planned transfusion within 2 months after the Screening Visit;
•    Serum  aspartate  aminotransferase  or  alanine  aminotransferase  >3    upper  limit  of 
normal (ULN); or
•    Total bilirubin >2  ULN, unless due to Gilbert’s syndrome;
20. Has uncontrolled diabetes with glycosylated hemoglobin >9.5% at the Screening Visit;
21. Is positive for HIV antibody, hepatitis C virus RNA, or hepatitis B surface antigen;
22. Has 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).
23. Has participated in another clinical study involving any investigational drug within 30 days
prior to the Screening Visit, or plans to participate in another clinical study within 30 days of
discontinuation of study drug;
24. Has received experimental therapy with a small molecule within 30 days of the Screening Visit
or 5 half-lives, whichever is longer, or received experimental therapy with a large molecule within
90 days of the Screening Visit or 5 half-lives, whichever is longer;
25. Has been on night shifts at any time during the 4 weeks before the Screening Visit and/or plans
to begin night shift at any time during the Screening and/or Double-Blind Treatment period;
26. Is pregnant, breastfeeding, or planning to become pregnant during the study; or
27. Is considered by the Investigator, after reviewing medical and psychiatric history, physical
examination, and laboratory evaluations, to be unsuitable for any other reason that may either
place the patient at increased risk during participation or interfere with the interpretation of
the study outcomes.
Randomization Criteria
Patients who meet all of the following

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Irina Bancos, M.D.

Contact us for the latest status

Contact information:

Stacy Anderson R.N.

(507) 266-6068

Anderson.Stacy@mayo.edu

More information

Publications

Publications are currently not available
.
CLS-20522391

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