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TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension

Primary Purpose

Refractory Hypertension

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Placebo

TC-5214

About this trial

This is an interventional treatment trial for Refractory Hypertension focused on measuring refractory hypertension, hypertension

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Any unstable medical condition other than hypertension;
Stage 3 hypertension (SBP > 180mmHg and/or DBP > 110mmHg);
Heart rate > 100 beats per minute;
WOCBP who is pregnant or who is planning to become pregnant during the study;
History within past year of alcohol or illicit drug abuse;
Unable to comply with study procedures in opinion of investigator;
Concomitant medications for any medical condition that is uncontrolled for more than 2 weeks prior to study entry;
Current use of alpha-adrenergic blocker, hydralazine, clonidine, guanethidine, guanadrel, or rauwolfia alkaloids;
History of myocardial infarction or angina pectoris;
Current seizure disorder;
Renal insufficiency as defined by a serum creatinine > 2.0;
Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency;
History of or concurrent ileus, glaucoma, or urinary retention;
Inability of subject to understand and sign the ICF;
Known systemic infection (HBV, HCV, HIV, TB);
Current use of smoking cessation therapy within 4 weeks of screening;
Use of herbal supplements;
Clinically significant finding on physical exam;
Clinically significant laboratory or ECG abnormality, including QTcF > 460 msec;
Participation in another clinical trial in last month;
Body Mass Index (BMI) > 35.
Body weight < 100 pounds.
Site staff or family member of study site staff.

Sites / Locations

Piedmont Medical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

1 mg TC-5214

2 mg TC-5214

4 mg TC-5214

8 mg TC-5214

Arm Description

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.

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

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

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.

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

Outcomes

Primary Outcome Measures

Mean difference between TC-5214 and placebo in change at 3 hours from baseline SBP

Secondary Outcome Measures

Safety and tolerability of TC-5214 in patients with refractory hypertension and obtain preliminary dose-response estimates

Full Information

NCT ID

NCT00899977

First Posted

May 8, 2009

Last Updated

September 3, 2013

Sponsor

Targacept Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00899977

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2013

Overall Recruitment Status

Terminated

Why Stopped

Business reasons

Study Start Date

May 2009 (undefined)

Primary Completion Date

August 2009 (Actual)

Study Completion Date

December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Targacept Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Refractory Hypertension

Keywords

refractory hypertension, hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

1 mg TC-5214

Arm Type

Experimental

Arm Description

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

Arm Title

2 mg TC-5214

Arm Type

Experimental

Arm Description

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

Arm Title

4 mg TC-5214

Arm Type

Experimental

Arm Description

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.

Arm Title

8 mg TC-5214

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo

Intervention Type

Drug

Intervention Name(s)

TC-5214

Primary Outcome Measure Information:

Title

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.

Secondary Outcome Measure Information:

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. Outpatient with stable housing. Subjects must be able to stay in the clinic for 8 hrs on Day 1, Day 8, Day 15, Day 22, and Day 36. Able to give and to sign informed consent. Exclusion Criteria: Any unstable medical condition other than hypertension; Stage 3 hypertension (SBP > 180mmHg and/or DBP > 110mmHg); Heart rate > 100 beats per minute; WOCBP who is pregnant or who is planning to become pregnant during the study; History within past year of alcohol or illicit drug abuse; Unable to comply with study procedures in opinion of investigator; Concomitant medications for any medical condition that is uncontrolled for more than 2 weeks prior to study entry; Current use of alpha-adrenergic blocker, hydralazine, clonidine, guanethidine, guanadrel, or rauwolfia alkaloids; History of myocardial infarction or angina pectoris; Current seizure disorder; Renal insufficiency as defined by a serum creatinine > 2.0; Uncontrolled hypothyroidism, vitamin B12 or folic acid deficiency; History of or concurrent ileus, glaucoma, or urinary retention; Inability of subject to understand and sign the ICF; Known systemic infection (HBV, HCV, HIV, TB); Current use of smoking cessation therapy within 4 weeks of screening; Use of herbal supplements; Clinically significant finding on physical exam; Clinically significant laboratory or ECG abnormality, including QTcF > 460 msec; Participation in another clinical trial in last month; Body Mass Index (BMI) > 35. Body weight < 100 pounds. Site staff or family member of study site staff.

Facility Information:

Facility Name

Piedmont Medical Research

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27101

Country

United States

12. IPD Sharing Statement

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TC-5214 as Augmentation Therapy in Patients With Refractory Hypertension

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