TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension

This study has been terminated.
(Business reasons)
Sponsor:
Information provided by (Responsible Party):
Targacept Inc.
ClinicalTrials.gov Identifier:
NCT00899977
First received: May 8, 2009
Last updated: September 3, 2013
Last verified: September 2013
  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
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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:


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
Study Completion Date: December 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects may receive a single, oral dose of placebo (capsule) in one of 4 crossover periods. Also, subjects may receive placebo orally, twice daily for 14 days in the last phase of the study.
Drug: Placebo
Matching placebo
Experimental: 1 mg TC-5214
Subjects may receive a single, oral capsule of 1 mg TC-5214 in one of 4 crossover periods.
Drug: TC-5214
Experimental: 2 mg TC-5214
Subjects may receive a single, oral capsule of 2 mg TC-5214 in one of 4 crossover periods.
Drug: TC-5214
Experimental: 4 mg TC-5214
Subjects may receive a single, oral capsule of 4 mg TC-5214 in one of 4 crossover periods. Also, subjects may receive 4 mg TC-5214 orally, twice daily for 14 days in the last phase of the study.
Drug: TC-5214
Experimental: 8 mg TC-5214
Subjects may receive a single, oral capsule of 8 mg TC-5214 in one of 4 crossover periods.
Drug: TC-5214

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:

  1. 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.
  2. 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.
  3. Outpatient with stable housing.
  4. Subjects must be able to stay in the clinic for 8 hrs on Day 1, Day 8, Day 15, Day 22, and Day 36.
  5. Able to give and to sign informed consent.

Exclusion Criteria:

  1. Any unstable medical condition other than hypertension;
  2. Stage 3 hypertension (SBP > 180mmHg and/or DBP > 110mmHg);
  3. Heart rate > 100 beats per minute;
  4. WOCBP who is pregnant or who is planning to become pregnant during the study;
  5. History within past year of alcohol or illicit drug abuse;
  6. Unable to comply with study procedures in opinion of investigator;
  7. Concomitant medications for any medical condition that is uncontrolled for more than 2 weeks prior to study entry;
  8. Current use of alpha-adrenergic blocker, hydralazine, clonidine, guanethidine, guanadrel, or rauwolfia alkaloids;
  9. History of myocardial infarction or angina pectoris;
  10. Current seizure disorder;
  11. Renal insufficiency as defined by a serum creatinine > 2.0;
  12. Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency;
  13. History of or concurrent ileus, glaucoma, or urinary retention;
  14. Inability of subject to understand and sign the ICF;
  15. Known systemic infection (HBV, HCV, HIV, TB);
  16. Current use of smoking cessation therapy within 4 weeks of screening;
  17. Use of herbal supplements;
  18. Clinically significant finding on physical exam;
  19. Clinically significant laboratory or ECG abnormality, including QTcF > 460 msec;
  20. Participation in another clinical trial in last month;
  21. Body Mass Index (BMI) > 35.
  22. Body weight < 100 pounds.
  23. Site staff or family member of study site staff.
  Contacts and Locations
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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.
ClinicalTrials.gov Identifier: NCT00899977     History of Changes
Other Study ID Numbers: TC-5214-23-CRD-002
Study First Received: May 8, 2009
Last Updated: September 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Targacept Inc.:
refractory hypertension
hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 22, 2014