TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension

NCT ID: NCT00899977

Last Updated: 2013-09-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2009-12-31

Brief Summary

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.

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.

Conditions

Refractory Hypertension

Keywords

refractory hypertension; hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo

1 mg TC-5214

Subjects may receive a single, oral capsule of 1 mg TC-5214 in one of 4 crossover periods.

Group Type: EXPERIMENTAL

TC-5214

Intervention Type: DRUG

2 mg TC-5214

Subjects may receive a single, oral capsule of 2 mg TC-5214 in one of 4 crossover periods.

Group Type: EXPERIMENTAL

TC-5214

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

TC-5214

Intervention Type: DRUG

8 mg TC-5214

Subjects may receive a single, oral capsule of 8 mg TC-5214 in one of 4 crossover periods.

Group Type: EXPERIMENTAL

TC-5214

Intervention Type: DRUG

Interventions

Placebo

Matching placebo

Intervention Type: DRUG

TC-5214

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Targacept Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Piedmont Medical Research

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

TC-5214-23-CRD-002

Identifier Type: -

Identifier Source: org_study_id