Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium (CHAMP)
Primary Purpose
Arterial Hypertension, Diabetes, Hypokalemia
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Cicletanine + magnesium
Cicletanine
Sponsored by
About this trial
This is an interventional treatment trial for Arterial Hypertension focused on measuring Cicletanine, Magnesium, Metabolic disease
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- Laboratory findings outside of normal range can be considered grounds for exclusion at the discretion of the Sponsor, Medical Monitor and / or Principal Investigator
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Cicletanine
Cicletanine + magnesium
Arm Description
Patients will take escalating doses of cicletanine
Patients will take escalating doses of cicletanine; patients will in addition take magnesium
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Reduction in systolic blood pressure vs. baseline
Aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
Reduction in diastolic blood pressure vs. baseline
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
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
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
The average potassium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Average levels of sodium in patients on cicletanine with and without magnesium
The average sodium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Average levels of magnesium in patients on cicletanine with and without magnesium
The average magnesium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Full Information
NCT ID
NCT02709031
First Posted
March 10, 2016
Last Updated
August 30, 2021
Sponsor
Navitas Pharma
Collaborators
IndiPharm Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02709031
Brief Title
Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium
Acronym
CHAMP
Official Title
Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 2022 (Anticipated)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Navitas Pharma
Collaborators
IndiPharm Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arterial Hypertension, Diabetes, Hypokalemia, Hyponatremia
Keywords
Cicletanine, Magnesium, Metabolic disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cicletanine
Arm Type
Active Comparator
Arm Description
Patients will take escalating doses of cicletanine
Arm Title
Cicletanine + magnesium
Arm Type
Experimental
Arm Description
Patients will take escalating doses of cicletanine; patients will in addition take magnesium
Intervention Type
Drug
Intervention Name(s)
Cicletanine + magnesium
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cicletanine
Intervention Description
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,
Primary Outcome Measure Information:
Title
Time to potassium rescue
Description
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.
Time Frame
13 weeks (duration of study)
Secondary Outcome Measure Information:
Title
Reduction in systolic blood pressure vs. baseline
Description
Aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
Time Frame
13 weeks (duration of study)
Title
Reduction in diastolic blood pressure vs. baseline
Description
Aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
Time Frame
13 weeks (duration of study)
Title
Reduction in HbA1c vs. baseline
Description
Aggregate measure made for all 24 patients (12 cicletanine + magnesium; 12 cicletanine only). Subgroup analyses will also be made as feasible.
Time Frame
13 weeks (duration of study)
Title
CRP (C reactive protein) levels
Description
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.
Time Frame
13 weeks (duration of study)
Title
Average levels of potassium in patients on cicletanine with and without magnesium
Description
The average potassium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Time Frame
13 weeks (duration of study)
Title
Average levels of sodium in patients on cicletanine with and without magnesium
Description
The average sodium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Time Frame
13 weeks (duration of study)
Title
Average levels of magnesium in patients on cicletanine with and without magnesium
Description
The average magnesium levels levels in the two groups (cicletanine + magnesium; cicletanine only) will be compared. Subgroup analyses will also be made as feasible.
Time Frame
13 weeks (duration of study)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Laboratory findings outside of normal range can be considered grounds for exclusion at the discretion of the Sponsor, Medical Monitor and / or Principal Investigator
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
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium
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