Clinical trial NCT00899977: TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Refractory Hypertension
Keywords: refractory hypertension
hypertension
Lead sponsor: Targacept Inc.
Sponsor class: INDUSTRY
First posted: 2009-05-12
Enrollment: 1
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: TREATMENT

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.

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.

Primary outcomes:
measure: Mean difference between TC-5214 and placebo in change at 3 hours from baseline SBP
timeFrame: 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.
Secondary outcomes:
measure: Safety and tolerability of TC-5214 in patients with refractory hypertension and obtain preliminary dose-response estimates
timeFrame: Days 1, 8, 15, 22 and 36
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Piedmont Medical Research
state: North Carolina
Study officials:
References: