TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension

• ClinicalTrials.gov Identifier: NCT00899977
• Recruitment Status: Terminated
• First Posted: May 12, 2009
• Last Update Posted: September 13, 2013
• Sponsor: Targacept Inc.
• Information provided by (Responsible Party): Targacept Inc.

Tracking Information

• First Submitted Date: May 8, 2009
• First Posted Date: May 12, 2009
• Last Update Posted Date: September 13, 2013
• Study Start Date: May 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 14, 2009): 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. ]
• Original Primary Outcome Measures (submitted: May 11, 2009): Mean difference between TC-5214 and placebo in change at 3 hours from baseline DBP [ 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. ]
• Current Secondary Outcome Measures (submitted: May 11, 2009): 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 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Refractory Hypertension

Intervention

• Drug: Placebo
  Matching placebo
• Drug: TC-5214

Study Arms

• 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.
  Intervention: Drug: Placebo
• Experimental: 1 mg TC-5214
  Subjects may receive a single, oral capsule of 1 mg TC-5214 in one of 4 crossover periods.
  Intervention: 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.
  Intervention: 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.
  Intervention: 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.
  Intervention: Drug: TC-5214

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 5, 2009): 1
• Original Estimated Enrollment (submitted: May 11, 2009): 12
• Actual Study Completion Date: December 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00899977
• Other Study ID Numbers: TC-5214-23-CRD-002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Targacept Inc.
• Original Responsible Party: Gaston Farr, MA, PMP, Targacept, Inc.
• Current Study Sponsor: Targacept Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Targacept Inc.
• Verification Date: September 2013