To Determine Blood Pressure Interaction Between TC-5214 and Anti-Hypertensive Medications (Calcium Channel Blockers, Beta Blockers, and ACE Inhibitors) in Patients With Chronic Hypertension

Study Overview
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Brief Summary
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This is a two part study. Part 1 will determine determine if administration of TC-5214 has an effect on sitting blood pressure in patients with chronic hypertension. Part 2 will determine any possible interactions between TC-5214 and Anti-Hypertensive Medications (Calcium Channel Blockers, Beta Blockers, and ACE Inhibitors).

Detailed Description
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A Phase I Randomised, Placebo-Controlled, Double-Blind Study in Hypertensive Patients of the Blood Pressure Interaction between TC-5214 and Anti-Hypertensive Medications (Calcium Channel Blockers, Beta Blockers, and ACE Inhibitors)

Official Title
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A Phase I Randomised, Placebo-Controlled, Double-Blind Study in Hypertensive Patients of the Blood Pressure Interaction Between TC-5214 and Anti-Hypertensive Medications (Calcium Channel Blockers, Beta Blockers, and ACE Inhibitors)

Conditions
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Chronic Hypertension

Intervention / Treatment
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* Drug: TC-5214
* Drug: TC-5214


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Male or female patients with chronic, stable hypertension treated for at least 1 month before screening with a calcium channel blocker, a beta blocker, or an ACE inhibitor, either as the only anti-hypertensive medication or concurrently with a diuretic. The patients should have no change in their current anti hypertensive treatment for at least 1 month before dosing Patients in Part 1 should have an SBP of ≤140 mmHg at screening and ≤160 mmHg at Visit 1a and pre-dose on Day 1 Patients in Part 2 should have an SBP of ≤160 mmHg at screening Visit 1 and pre dose on Day 1. Systolic blood pressure and DBP should not vary by more than 8 mmHg and 5 mmHg, respectively, in the pre-dose period (screening, Visit 1a, and pre-dose on Day 1) Age 18 to 65 years (inclusive) Exclusion Criteria: Other than having chronic hypertension, the history of any clinically significant medical, neurologic, or psychiatric disease or disorder which, in the opinion of the Investigator and/or the Sponsor, may either put the patient at risk because of participation in the study or influence the results, or the patient's ability to participate in the study. Patients with dyslipidaemia (diet controlled or treated with a statin) and/or metabolic syndrome (diet controlled or treated with metformin) may be entered into the study Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the investigational product Patients with a pre-treatment SBP (if known) of >180 mmHg or a history of accelerated or malignant hypertension based on grade III (hypertensive haemorrhages and/or cotton wool spots) or grade IV (hypertensive papilloedema) retinopathy at any time History or presence of gastrointestinal (including irritable bowel disease), hepatic, or renal disease (creatinine clearance of ≤50 mL/minute calculated using the Cockcroft Gault equation) or any other condition known to interfere with the ADME of the investigational product. Patients with a history of surgery on the gastrointestinal tract (not including appendectomy or cholecystectomy) should also be excluded Any significant ECG abnormality including QTcF prolongation (>450 ms) or significant arrhythmias, or junctional rhythms

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>TC-5214 | Drug: TC-5214<br>* Tablet oral bid days 1 to 7<br>|
| Experimental: 2<br>TC-5214 with placebo | Drug: TC-5214<br>* Tablet oral bid days 8 to 14<br>|
| Experimental: 3<br>TC-5214 with placebo | Drug: TC-5214<br>* Tablet oral bid days 1 to 7<br>|
| Experimental: 4<br>TC-5214 | Drug: TC-5214<br>* Tablet oral bid days 8 to 14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: To measure the effect of TC-5214 on sitting blood pressure in patients with chronic hypertension. | The following assessments will be measured and reported: - A change from baseline in blood pressure and pulse rate. | Day 1 through to follow up | 
| Part 2: To measure the effect of TC-5214 combined with treatment with the common classes of anti-hypertensive medication (calcium channel blockers, beta blockers, angiotensin converting enzyme inhibitors) on sitting blood pressure. | The following assessments will be measured and reported: A change from baseline in blood pressure and pulse rate. | Day 1 through to follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine the safety and tolerability of TC-5214. | The following assessments will be measured and reported: The number of particpants with adverse events A change from baseline in blood pressure and pulse rate A change from baseline in laboratory assessments A change from baseline in vital signs A change from baseline in electrocardiogram (ECG) A change from baseline in physical examination | Day 1 through to Follow up | 
| The concentration of TC-5214 in plasma will be measured. |  | Day 1 to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Randomised, Placebo-Controlled, Double-Blind,Hypertensive Patients, Blood Pressure, Calcium Channel Blockers, Beta Blockers, ACE Inhibitors, Scientific terminology: To determine if treatment with TC5214 alone or in combination with Anti-Hypertensive Medications has an effect on sitting blood pressure, Laymen terminology: Hypertension