To Compare the Pharmacokinetics of a Single Oral Dose of TC-5214 in Subjects With Renal Impairment and With Subjects With Normal Renal Function

NCT01240967 | Completed Phase 1

• 1 other identifier: D4130C00008
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to compare the absorption and distribution of a single oral dose of TC-5214 in subjects with renal impairment and with subjects with normal renal function.

Conditions

Healthy Volunteers; Patients; Pharmacokinetics; Renal Impairment

Keywords

Phase 1; healthy volunteers; volunteers with renal impairment; pharmacokinetics; TC-5214

Outcome Measures

Primary Outcomes (2)

• The pharmacokinetics (PK) of a single dose of TC-5214 in subjects with renal impairment in comparison to the results in subjects with normal renal function

  For Group 1, Group 2, and Group 3 blood PK samples will be collected at predose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose.

• The pharmacokinetics (PK) of a single dose of TC-5214 in subjects with renal impairment in comparison to the results in subjects with normal renal function

  If study procedures for any subjects in Group 4 are extended by 24 hours to Day 5, PK samples will be collected at predose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours postdose.

  For Group 4 blood PK samples will be collected at predose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose.

Secondary Outcomes (2)

• The effect of hemodialysis on TC-5214 pharmacokinetics

  For Group 5 blood PK samples will be collected at predose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, and 72 hours postdose.

• Safety and tolerability variables: Adverse events and serious adverse events (including severity), vital signs, physical examinations, laboratory parameters, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.

  A range of 5 days -from Screening to follow-up visit.

Interventions

TC-5214 DRUG

Oral tablets, single dose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and non-pregnant, non-lactating females 18 to 80 years old inclusive with suitable veins for cannulation or repeated venipuncture with a weight of at least 50 kg.
• Regarding renal function, subjects will be classified as either normal or as suffering from mild, moderate or severe renal impairment. Classification of renal impairment will be based using an abbreviated 4 variable Modified Diet in Renal Disease (MDRD) equations. To ensure the assessment of consistent estimated glomerular filtration rate (eGFR) using the MDRD, a single equation will be used (see Section 6.2)
• Negative screen for Human Immunodeficiency Virus and negative results for serum hepatitis B surface antigen
• Regarding renal function, subjects will be classified as either normal or as suffering from mild, moderate or severe renal impairment. Classification of renal impairment will be based using an abbreviated 4 variable MDRD equation. To ensure the assessment of consistent estimated glomerular filtration rate (eGFR) using the MDRD, a single equation will be used.

You may not qualify if:

• History of any clinically significant medical, neurologic or psychiatric disease or disorder (other than those previously defined as acceptable for these population) which, in the opinion of the Investigator and sponsor, may either put the subject at risk because of participation in the study, or influence the results of the subject's ability to participate in the study: This includes seizure activity and repeated episodes of major depression.
• Subjects with a history of suicide attempts in the past year and/or seen by the Investigator as having a significant history of risk of suicide or homicide, or considered at risk for suicide or homicide during the study
• Subjects with an active renal transplant (subjects who have previously received a renal transplant and are currently undergoing dialysis due to transplant failure may be enrolled)
• Any clinically significant acute illness or medical/surgical procedure within 4 weeks of the first administration of investigational product (IP) (other than those previously defined as acceptable for these population) as judged by the Investigator.
• Positive test in drugs of abuse screens (except for prescription medications, which are verified by the Investigator), or alcohol on admission to the clinic prior to the administration of the IP

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Orlando, Florida, United States

Location

Research site

Minneapolis, Minnesota, United States

Location

Related Publications (2)

• Alverlind S, Barassin S, Dalen P, Li Y, Toler S, Eriksson H, Tummala R. Clinical pharmacokinetics of the nicotinic channel modulator dexmecamylamine (TC-5214) in subjects with various degrees of renal impairment. Clin Drug Investig. 2014 Jul;34(7):457-65. doi: 10.1007/s40261-014-0195-0.

  PMID: 24760402 DERIVED

• Xu H, Henningsson A, Alverlind S, Tummala R, Toler S, Beaver JS, Al-Huniti N. Population pharmacokinetics of TC-5214, a nicotinic channel modulator, in phase I and II clinical studies. J Clin Pharmacol. 2014 Jun;54(6):707-18. doi: 10.1002/jcph.264. Epub 2014 Jan 16.

  PMID: 24408516 DERIVED

Related Links

• Related Info
• CSR-D4130C00008.pdf
• D4130C00008/Clinical Study Protocol

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Hans A Eriksson, MD

  AstraZeneca

  STUDY DIRECTOR

• Thomas Marbury, MD

  Orlando Clinical Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 15, 2010
• Study Start: November 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: March 17, 2014

Record last verified: 2014-03

Locations

US (2)