TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension

Refractory Hypertension Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00899977
• Other study ID #: TC-5214-23-CRD-002
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: May 8, 2009
• Last updated: September 3, 2013
• Start date: May 2009
• Est. completion date: December 2009

Study information

• Verified date: September 2013
• Source: Targacept Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: December 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Hypertension
• Refractory Hypertension

Intervention

Drug:
• Placebo
Matching placebo
• TC-5214

Locations

Country	Name	City	State
United States	Piedmont Medical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Targacept Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean difference between TC-5214 and placebo in change at 3 hours from baseline SBP		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.	Yes
Secondary	Safety and tolerability of TC-5214 in patients with refractory hypertension and obtain preliminary dose-response estimates		Days 1, 8, 15, 22 and 36	Yes