TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension - Full Text View

Sponsored by:	Targacept Inc.
Information provided by:	Targacept Inc.
ClinicalTrials.gov Identifier:	NCT00899977

Purpose

A pilot study of subjects with refractory hypertension (on 3 concomitant agents with SBP > 140 mmHg and a DBP > 90 mmHg) randomized in a double-blind fashion to receive 4 single escalating doses of study medication in clinic.

Condition	Intervention	Phase
Refractory Hypertension	Drug: Placebo Drug: TC-5214 1 mg Drug: TC-5214 2mg Drug: TC-5214 4mg Drug: TC-5214 8mg	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study
Official Title:	A Double-blind, Randomized, Placebo-controlled, Sequential Group Pilot Study to Assess Safety, Tolerability, and Effectiveness of TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

U.S. FDA Resources

Further study details as provided by Targacept Inc.:

Primary Outcome Measures:

Mean difference between TC-5214 and placebo in change at 3 hours from baseline SBP [ Time Frame: Following dosing, 3 manual seated BP measurements and orthostatic BP measurements will be obtained in an identical fashion, at 30 minutes post-dose and at 1, 2, 3, 4, 5, 6, 7, and 8 hrs post-dose. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety and tolerability of TC-5214 in patients with refractory hypertension and obtain preliminary dose-response estimates [ Time Frame: Days 1, 8, 15, 22 and 36 ] [ Designated as safety issue: Yes ]

Enrollment:	1
Study Start Date:	May 2009
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator	Drug: Placebo Matching placebo
TC-5214 1mg: Experimental	Drug: TC-5214 1 mg Free base 1 mg capsule
TC-5214 2mg: Experimental	Drug: TC-5214 2mg Free base 2mg capsule
TC-5214 4mg: Experimental	Drug: TC-5214 4mg Free base 4mg capsule
TC-5214 8mg: Experimental	Drug: TC-5214 8mg 2 free base 4mg capsules

Detailed Description:

12 subjects with refractory hypertension will be randomized in a double-blind fashion to receive single escalating doses of study medication in-clinic: on Day 1 (1mg), Day 8 (2mg), Day 15 (4mg) and Day 22 (8mg). On each of these 4 days, 10 subjects will receive TC-5214, and 2 subjects will receive placebo. Placebo treatments will be pooled across the 4 days of single-dose to produce an equivalent reference cohort (n = 8) for each treatment dose (n=10). Following the single-dose administration of 8mg in the clinic on Day 22, subjects will continue with two weeks (Days 23 - 35) of outpatient self-administration of TC-5214 (4mg BID; n = 6), or matching placebo (BID; n = 6). On Day 36, subjects will return for a final in-clinic dose of either TC-5214 (4mg, n = 6) or placebo (n = 6). There will be a 1-week follow-up period at the end of the treatment period.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Refractory hypertension, defined as a SBP of >140mmHg and a DBP > 90mmHg, on stable doses of at least 3 concomitant antihypertensive treatment (which must include a diuretic and an ACEI, ARB or RA) for 8 weeks prior to Screening. All approved antihypertensive treatments are allowed except for alpha-adrenergic blockers, hydralazine, clonidine, guanethidine, guanadrel, and rauwolfia alkaloids.
Stable hypertension, as defined by: a. mean SBP on Day -7 that is within 20mmHg of the mean SBP on Day 1, with both mean SBPs > 140mmHg; and b. mean DBP on Day -7 that is within 10mm of the mean DBP on Day 1, with both mean DBPs > 90mmHg.
Outpatient with stable housing.
Subjects must be able to stay in the clinic for 8 hrs on Day 1, Day 8, Day 15, Day 22, and Day 36.
Able to give and to sign informed consent.

Exclusion Criteria:

Any unstable medical condition other than hypertension;
Stage 3 hypertension (SBP > 180mmHg and/or DBP > 110mmHg);
Heart rate > 100 beats per minute;
WOCBP who is pregnant or who is planning to become pregnant during the study;
History within past year of alcohol or illicit drug abuse;
Unable to comply with study procedures in opinion of investigator;
Concomitant medications for any medical condition that is uncontrolled for more than 2 weeks prior to study entry;
Current use of alpha-adrenergic blocker, hydralazine, clonidine, guanethidine, guanadrel, or rauwolfia alkaloids;
History of myocardial infarction or angina pectoris;
Current seizure disorder;
Renal insufficiency as defined by a serum creatinine > 2.0;
Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency;
History of or concurrent ileus, glaucoma, or urinary retention;
Inability of subject to understand and sign the ICF;
Known systemic infection (HBV, HCV, HIV, TB);
Current use of smoking cessation therapy within 4 weeks of screening;
Use of herbal supplements;
Clinically significant finding on physical exam;
Clinically significant laboratory or ECG abnormality, including QTcF > 460 msec;
Participation in another clinical trial in last month;
Body Mass Index (BMI) > 35.
Body weight < 100 pounds.
Site staff or family member of study site staff.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00899977

Locations

United States, North Carolina
Piedmont Medical Research
Winston-Salem, North Carolina, United States, 27101

Sponsors and Collaborators

Targacept Inc.

More Information

No publications provided

Responsible Party:	Targacept, Inc. ( Gaston Farr, MA, PMP )
Study ID Numbers:	PRO-05214-CRD-002
Study First Received:	May 8, 2009
Last Updated:	August 5, 2009
ClinicalTrials.gov Identifier:	NCT00899977 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Targacept Inc.:

refractory hypertension
hypertension

Study placed in the following topic categories:

Vascular Diseases
Hypertension

Additional relevant MeSH terms:

Vascular Diseases
Cardiovascular Diseases
Hypertension

ClinicalTrials.gov processed this record on September 11, 2009