Pharmacokinetics of Tasimelteon in Subjects With Renal Impairment and Matched Control Subjects With Relatively Normal Renal Function

NCT01526746 | Completed Phase 1

• 1 other identifier: VP-VEC-162-1106
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research study is to understand whether there is any difference in the amount of tasimelteon (including its breakdown products) in the blood of individuals with severe renal impairment compared to individuals who have normal renal function. The safety and tolerability of tasimelteon will also be assessed throughout this study.

Conditions

Renal Impairment

Keywords

End stage renal disease; ESRD; kidney disease; renal impairment; renal

Outcome Measures

Primary Outcomes (1)

• Tasimelteon pharmacokinetic parameters (AUC, Cmax, Tmax)

  Predose, 0.25, 1, 1.5, 2, 4, 6, 8, 12, 24, 30, and 36 hours post-dose

Secondary Outcomes (5)

• Pharmacokinetic parameters (AUC, Cmax, Tmax) of tasimelteon metabolites M3, M9, M11, M12, M13, and M14

  Predose, 0.25, 1, 1.5, 2, 4, 6, 8, 12, 24, 30, and 36 hours post-dose

• The percentage of tasimelteon and its metabolites that are removed by hemodialysis (AUC)

  4, 6, 8 hours after dosing

• The ratio of plasma protein bound versus unbound fractions of tasimelteon and metabolites M9, M11, M12, M13, and M14

  0.5 and 3 hours post dose

• Safety and tolerability as measured by spontaneous reporting of AEs, and clinically significant changes in laboratory parameters, ECG parameters, and vital signs

  36 hours

• The Columbia-Suicide Severity Rating Scale will be used to assess suicidal behavior and ideation.

  once per day at Screening (approximately day -7), Day -1 (baseline), Day 2 (end of study)

Study Arms (3)

End Stage Renal Disease, dialysis

EXPERIMENTAL

eGFR \<15 ml/min/1.73m\^2

Drug: Tasimelteon

Severe renal impairment

EXPERIMENTAL

eGFR \< 29 ml/min/1.73m\^2

Drug: Tasimelteon

Healthy controls

EXPERIMENTAL

eGFR \> 80 mL/min/1.73m\^2 Matched to renally impaired subjects by age, gender, BMI, and smoking status

Drug: Tasimelteon

Interventions

Tasimelteon DRUG

20mg capsule, once

Also known as: VEC-162

End Stage Renal Disease, dialysis; Healthy controls; Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Groups 1-3
• Ability and acceptance to provide written informed consent;
• Men or women between 18 - 79 years, inclusive;
• Subjects with Body Mass Index (BMI) of \>18 and \<40 kg/m2 (BMI = weight (kg)/ \[height (m)\]2);
• Males, non-fecund females (i.e., surgically sterilized, if procedure was done 6 months before screening or subject is postmenopausal, without menses for 6 months before screening), or females of child-bearing potential using an acceptable method of birth control for a period of 35 days before the first dosing and have a negative pregnancy test at the screening and baseline visits; Note 1: Acceptable methods of birth control include any one of the following: abstinence, vasectomized sexual partner, hormonal methods (i.e. pill, hormonal IUD, Depo-Provera, implants, patch, intravaginal device \[NuvaRing\]), intrauterine device (IUD \[copper banded coils\]), diaphragm, cervical cap, or condom with spermicidal jelly or foam.
• Willing and able to comply with study requirements and restrictions;
• Groups 1- 2 (renal impairment)
• Subjects with renal impairment defined as
• Group 1: Stage 5 End Stage Renal Disease (ESRD) (eGFR \< 15 mL/min/m2) requiring regularly scheduled dialysis and have been on a stable dialysis regimen for at least three months at baseline; OR
• Group 2: Stage 4 severe renal impairment (eGFR ≤ 29 mL/min/m2) but not requiring dialysis as calculated using the Modification of Diet in Renal Disease (MDRD) Equation (Appendix 18.3)
• Otherwise considered healthy in general as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening;
• Vital signs (after 3 minutes resting in a semi-supine position) which are within the ranges shown below.
• Body temperature between 35.0-37.5 °C;
• Systolic blood pressure between 100-180 mmHg;
• Diastolic blood pressure between 60-115 mmHg;

You may not qualify if:

• Groups 1-3
• Smokers (use of tobacco products in the previous 3 months) unable or unwilling to limit consumption to 10 cigarettes per day or less while checked into the inpatient facility.
• a. Note: Smoking will be a match criteria and the site should attempt to enroll an equal number of smokers and non-smokers into each group.
• Exposure to any investigation drug, including placebo, within 30 days or 5 half-lives (whichever is longer) of dosing;
• Donation or loss of 400 mL or more of blood within two months prior to dosing;
• Significant illness within the two weeks prior to dosing;
• Answer 'yes' to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS, or answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the "Suicidal Behavior" portion of the Columbia Suicide Severity Rating Scale (C-SSRS); and the ideation or behavior occurred within the past 6 months;
• Functioning renal transplant;
• History within the past 2 years of clinically significant acute or chronic bronchospastic disease, including asthma and chronic obstructive pulmonary disease, treated or not treated;
• Treatment with any drug known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 day preceding the Screening visit;
• Participation in a previous BMS-214778/VEC-162 trial;
• History of drug or alcohol abuse as defined in DSM-IV, Diagnostic Criteria for Drug and Alcohol Abuse, within the 12 months prior to screening or evidence of such abuse as indicated by the laboratory assays conducted during the screening and baseline visits. A positive drug screen in Groups 1 and 2 is acceptable if there is documentation that subjects have been prescribed the corresponding medication;
• History of immunocompromise, including a positive HIV (ELISA and Western blot) test result;
• A positive Hepatitis B surface antigen (HBsAg) test result;
• Any surgical or medical condition which might significantly alter the absorption, distribution or excretion of any drug. The Investigator should be guided by evidence of any of the following:

Sponsors & Collaborators

• Vanda Pharmaceuticals: lead

Study Sites (3)

Clinical Pharmacology of Miami, Inc.

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, United States

Location

MeSH Terms

Conditions

Renal Insufficiency; Kidney Failure, Chronic; Kidney Diseases

Interventions

tasimelteon

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2012
• First Posted: February 6, 2012
• Study Start: February 1, 2012
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: February 17, 2014

Record last verified: 2014-02

Locations

US (3)