Clinical trial NCT02709031: Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium
Official title: Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Arterial Hypertension
Diabetes
Hypokalemia
Hyponatremia
Keywords: Cicletanine
Magnesium
Metabolic disease
Lead sponsor: Navitas Pharma
Sponsor class: INDUSTRY
Collaborators: name: IndiPharm Inc.
First posted: 2016-03-15
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to potassium rescue
timeFrame: 13 weeks (duration of study)
Secondary outcomes:
measure: Reduction in systolic blood pressure vs. baseline
timeFrame: 13 weeks (duration of study)
measure: Reduction in diastolic blood pressure vs. baseline
timeFrame: 13 weeks (duration of study)
measure: Reduction in HbA1c vs. baseline
timeFrame: 13 weeks (duration of study)
measure: CRP (C reactive protein) levels
timeFrame: 13 weeks (duration of study)
measure: Average levels of potassium in patients on cicletanine with and without magnesium
timeFrame: 13 weeks (duration of study)
measure: Average levels of sodium in patients on cicletanine with and without magnesium
timeFrame: 13 weeks (duration of study)
measure: Average levels of magnesium in patients on cicletanine with and without magnesium
timeFrame: 13 weeks (duration of study)
Other outcomes:
Locations:
Study officials:
References: