Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium

NCT02709031 | Unknown Phase 1 FDA Drug

• 1 other identifier: NAV-011
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Cicletanine, which has been approved and launched for hypertension in France and Germany, has promise beyond hypertension in critically-unmet needs such as diabetes. It is evident from in vitro, animal and human studies that cicletanine's optimal dose in diabetes and other challenging, critically-unmet needs is likely to be higher than that for hypertension. Cicletanine's maximum tolerated dosage is not known, but the drug's dose-limiting effects are documented to be potassium loss and sodium loss from thiazide-type activity (one of the therapeutic mechanisms the drug is known to have); such thiazide-type losses are known to be reversed safely by magnesium. This trial explores the ability of magnesium to enhance cicletanine safety at higher doses in a trial involving patients with hypertension complicated by diabetes.

Conditions

Arterial Hypertension; Diabetes; Hypokalemia; Hyponatremia

Keywords

Cicletanine; Magnesium; Metabolic disease

Outcome Measures

Primary Outcomes (1)

• Time to potassium rescue

  The primary endpoint is the preservation of potassium levels at or above 3.3 mEq/L (milliequivalents per liter). A time to event model using the Log Rank test will be used to compare the Mg Group and those in the Non-Mg Group.

  13 weeks (duration of study)

Secondary Outcomes (7)

• Reduction in systolic blood pressure vs. baseline

  13 weeks (duration of study)

• Reduction in diastolic blood pressure vs. baseline

  13 weeks (duration of study)

• Reduction in HbA1c vs. baseline

  13 weeks (duration of study)

• CRP (C reactive protein) levels

  13 weeks (duration of study)

• Average levels of potassium in patients on cicletanine with and without magnesium

  13 weeks (duration of study)

Study Arms (2)

Cicletanine

ACTIVE COMPARATOR

Patients will take escalating doses of cicletanine

Drug: Cicletanine

Cicletanine + magnesium

EXPERIMENTAL

Patients will take escalating doses of cicletanine; patients will in addition take magnesium

Drug: Cicletanine + magnesium

Interventions

Cicletanine + magnesium DRUG

Cicletanine is an orally-dosed furopyridine drug launched or hypertension in France in 1988 (and soon thereafter in Germany by IPSEN. While the drug's maximum tolerated dose is not known, the principal concern (and so far only material concern) at higher doses is the decrease in levels of sodium and potassium. Trials so far have take n the drug up to 400 mg QD (once daily); it was well tolerated at that dose. The drug has had an excellent safety profile in its \~1.8 million patient-years of post-launch experience, Magnesium is being added to cicletanine in order to decrease losses of potassium and sodium, thereby enhancing cicletanine's safety at higher doses.

Cicletanine + magnesium

Cicletanine DRUG

Cicletanine is an orally-dosed furopyridine drug launched or hypertension in France in 1988 (and soon thereafter in Germany by IPSEN. While the drug's maximum tolerated dose is not known, the principal concern (and so far only material concern) at higher doses is the decrease in levels of sodium and potassium. Trials so far have take n the drug up to 400 mg QD; it was well tolerated at that dose. The drug has had an excellent safety profile in its \~1.8 million patient-years of post-launch experience,

Cicletanine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sitting SBP (systolic blood pressure) \> 150 mmHg (millimeters of mercury) after five minutes' rest.
• Type II diabetes, with HbA1c between 8.5 and 11.5%. If a patient at screening presents outside of this range, the investigator may elect to re-screen a patient once to determine further the patient's eligibility.
• Age \>18 and \< 80 years of age
• BMI between 20 and 35, inclusive
• Have been stable on existing therapy for at least 30 days prior to initiation of cicletanine (Visit 2)
• a. no change in antihypertensive nor antihyperglycemia agent dose within 30 days prior to screening visit.
• Willing to comply with the requirements of the protocol.
• Willing to provide written Informed Consent to participate in the study approved by an appropriately constituted IRB (Institutional Review Board).
• All females who are not post-menopausal should be using at least two forms of contraception during the entire study.

You may not qualify if:

• Use of potassium supplementation over the past 30 days
• Use of potassium-wasting diuretics, e. g., thiazides over the past 30 days
• AST (aspartate aminotransferase; also abbreviated SGOT) outside normal range of 5 and 40 mg/dL inclusive
• ALT (alanine aminotransferase; also abbreviated SGPT) outside normal range of 7 and 56 mg/dL inclusive
• History of or positive laboratory test for HIV, HBV (hepatitis B virus) or HCV (hepatitis C virus)
• Clinically significant psychiatric, addictive or neurologic disease or any other condition that, in the Investigator's opinion, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the requirements of the study protocol
• Evidence of unstable cardiovascular disease including intermittent atrial fibrillation or unstable angina within the 4 weeks prior to screening
• History of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention within the last 3 months
• Clinically significant valvular heart disease in the opinion of the Investigator
• History of cerebrovascular accident or transient ischemic attack within the last 3 months
• Presence or history of malignancy that required significant medical intervention within the preceding 3 months and/or is likely to result in death within the next 2 years
• Chronic renal impairment or renal insufficiency defined by a serum creatinine ³ 2.5 mEq/dL and/or the requirement for dialysis
• The subject is lactating, breastfeeding, or pregnant
• The subject has received any investigational medication within 30 days prior to the start of this study or be scheduled to receive another investigational drug during the course of this study

Sponsors & Collaborators

• Navitas Pharma: lead
• IndiPharm Inc.: collaborator

MeSH Terms

Conditions

Hypertension; Diabetes Mellitus; Hypokalemia; Hyponatremia; Metabolic Diseases

Interventions

cicletanine; Magnesium

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Endocrine System Diseases; Water-Electrolyte Imbalance

Intervention Hierarchy (Ancestors)

Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: March 15, 2016
• Study Start: June 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: September 1, 2024
• Last Updated: September 5, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share