Clinical trial NCT01403922: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Hypertension
Keywords: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-07-27
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Part 1: To measure the effect of TC-5214 on sitting blood pressure in patients with chronic hypertension.
timeFrame: Day 1 through to follow up
measure: 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.
timeFrame: Day 1 through to follow up
Secondary outcomes:
measure: To examine the safety and tolerability of TC-5214.
timeFrame: Day 1 through to Follow up
measure: The concentration of TC-5214 in plasma will be measured.
timeFrame: Day 1 to day 28
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Willingboro
country: United States
facility: Research Site
state: New Jersey
city: Berlin
country: Germany
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca PharmaceuticalsKvarnbergagatan 12, 15185, Sodertalje, Sweden
name: Hans A Eriksson, MD, PhD, MBA
role: STUDY_DIRECTOR
affiliation: Quintiles Drug Research Unit at Guy's HospitalQuintiles Limited6 Newcomen StreetLondon SE1 1YR
name: James Ritter, MD,FRCP FFPM
role: PRINCIPAL_INVESTIGATOR
References: