La ciclétanine dans l'hypertension avec diabète : le magnésium ajouté préserve le potassium et le sodium (CHAMP)
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.
Aperçu de l'étude
Statut
Statut
Les conditions
Les conditions
Intervention / Traitement
Intervention / Traitement
Type d'étude
Type d'étude
Phase
Phase
- Phase 2
- La phase 1
Critères de participation
Critère d'éligibilité
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
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Sitting SBP (systolic blood pressure) > 150 mmHg (millimeters of mercury) after five minutes' rest.
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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.
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Age >18 and < 80 years of age
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BMI between 20 and 35, inclusive
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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.
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Willing to comply with the requirements of the protocol.
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Willing to provide written Informed Consent to participate in the study approved by an appropriately constituted IRB (Institutional Review Board).
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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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Nombre de bras
Armes et Interventions
Groupe de participants / BrasGroupe de participants / Bras |
Intervention / TraitementIntervention / Traitement |
|---|---|
|
Comparateur actif: Cicletanine
Patients will take escalating doses of cicletanine |
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, |
|
Expérimental: Cicletanine + magnesium
Patients will take escalating doses of cicletanine; patients will in addition take magnesium |
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. |
Que mesure l'étude ?
Principaux critères de jugement
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Time to potassium rescue
Délai: 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. |
13 weeks (duration of study)
|
Mesures de résultats secondaires
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Reduction in systolic blood pressure vs. baseline
Délai: 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. |
13 weeks (duration of study)
|
|
Reduction in diastolic blood pressure vs. baseline
Délai: 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. |
13 weeks (duration of study)
|
|
Reduction in HbA1c vs. baseline
Délai: 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. |
13 weeks (duration of study)
|
|
CRP (C reactive protein) levels
Délai: 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. |
13 weeks (duration of study)
|
|
Average levels of potassium in patients on cicletanine with and without magnesium
Délai: 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. |
13 weeks (duration of study)
|
|
Average levels of sodium in patients on cicletanine with and without magnesium
Délai: 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. |
13 weeks (duration of study)
|
|
Average levels of magnesium in patients on cicletanine with and without magnesium
Délai: 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. |
13 weeks (duration of study)
|
Collaborateurs et enquêteurs
Parrainer
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Début de l'étude
Achèvement primaire (Estimé)
Achèvement primaire
Achèvement de l'étude (Estimé)
Achèvement de l'étude
Dates d'inscription aux études
Première soumission
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimé)
Première publication
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour publiée
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies du système endocrinien
- Maladies vasculaires
- Maladies cardiovasculaires
- Troubles du métabolisme du glucose
- Déséquilibre eau-électrolyte
- Maladies nutritionnelles et métaboliques
- Hypertension
- Diabète sucré
- Maladies métaboliques
- Hyponatrémie
- Hypokaliémie
- Produits chimiques inorganiques
- Éléments
- Métaux, lumière
- Métaux
- Métaux, terre alcaline
- Magnésium
- cicletanine
Autres numéros d'identification d'étude
Autres numéros d'identification d'étude
- NAV-011
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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