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

Phase 1

Not yet recruiting

• Conditions: Arterial Hypertension; Hypokalemia; Hyponatremia; Diabetes
• Interventions: Drug: Cicletanine + magnesium; Drug: Cicletanine

• Registration Number: NCT02709031
• Lead Sponsor: Navitas Pharma

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-10
• Study First Submitted QC: 2016-03-10
• Study First Posted: 2016-03-15
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-30
• Last Update Posted: 2021-09-05
• Study Start: 2022-06
• Primary Completion: 2024-06
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Sitting SBP (systolic blood pressure) > 150 mmHg (millimeters of mercury) after five minutes' rest.

2. 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.

3. Age >18 and < 80 years of age

4. BMI between 20 and 35, inclusive

5. 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.

6. Willing to comply with the requirements of the protocol.

7. Willing to provide written Informed Consent to participate in the study approved by an appropriately constituted IRB (Institutional Review Board).

8. All females who are not post-menopausal should be using at least two forms of contraception during the entire study.

Exclusion Criteria

1. Use of potassium supplementation over the past 30 days
2. Use of potassium-wasting diuretics, e. g., thiazides over the past 30 days
3. AST (aspartate aminotransferase; also abbreviated SGOT) outside normal range of 5 and 40 mg/dL inclusive
4. ALT (alanine aminotransferase; also abbreviated SGPT) outside normal range of 7 and 56 mg/dL inclusive
5. Laboratory findings outside of normal range can be considered grounds for exclusion at the discretion of the Sponsor, Medical Monitor and / or Principal Investigator
6. History of or positive laboratory test for HIV, HBV (hepatitis B virus) or HCV (hepatitis C virus)
7. 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
8. Evidence of unstable cardiovascular disease including intermittent atrial fibrillation or unstable angina within the 4 weeks prior to screening
9. History of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention within the last 3 months
10. Clinically significant valvular heart disease in the opinion of the Investigator
11. History of cerebrovascular accident or transient ischemic attack within the last 3 months
12. 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
13. Chronic renal impairment or renal insufficiency defined by a serum creatinine ³ 2.5 mEq/dL and/or the requirement for dialysis
14. The subject is lactating, breastfeeding, or pregnant
15. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cicletanine + magnesium	Cicletanine + magnesium	Patients will take escalating doses of cicletanine; patients will in addition take magnesium
Cicletanine	Cicletanine	Patients will take escalating doses of cicletanine

Primary Outcome Measures

Name	Time	Method
Time to potassium rescue	13 weeks (duration of study)	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.

Secondary Outcome Measures

Name	Time	Method
Average levels of sodium in patients on cicletanine with and without magnesium	13 weeks (duration of study)	The average sodium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Reduction in systolic blood pressure vs. baseline	13 weeks (duration of study)	Aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
Reduction in HbA1c vs. baseline	13 weeks (duration of study)	Aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
Average levels of magnesium in patients on cicletanine with and without magnesium	13 weeks (duration of study)	The average magnesium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Reduction in diastolic blood pressure vs. baseline	13 weeks (duration of study)	Aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
CRP (C reactive protein) levels	13 weeks (duration of study)	CRP (C-reactive protein) is a measure of general inflammation.; This will be an aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
Average levels of potassium in patients on cicletanine with and without magnesium	13 weeks (duration of study)	The average potassium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.