Single-dose Pharmacokinetics and Safety of Oral Lofexidine in Renally-Impaired Subjects

NCT02313103 | Completed Phase 1

• 2 other identifiers: USWM-LX1-10081R01DA030916
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open-label, parallel-group, single-dose study of lofexidine in 8 adult subjects with ESRD maintained on hemodialysis (3 times per week) and 8 control subjects with normal renal function, recruited as 1:1 matches to each ESRD subjects, matched for gender, age, and BMI.

Conditions

Renally Impaired Subjects

Keywords

ESRD; End Stage Renal Disease; Normal Healthy Volunteers; Renally Impaired

Outcome Measures

Primary Outcomes (1)

• PK Profile

  Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae

  pre dose until 156 hours post dose

Secondary Outcomes (5)

• Adverse events

  screening through day 7 or 8

• Clinical laboratory tests

  screening through day 7 or 8

• Vital signs

  screening through day 7 or 8

• 12-lead ECG

  screening through day 7 or 8

• holter ECG

  screening through day 7 or 8

Study Arms (2)

Lofexidine HCl

OTHER

End Stage Renal Disease (ESRD) subjects will be dosed with 400 micrograms of lofexidine HCl with 240 mL water after their hemodialysis session.

Drug: lofexidine HCl

Matched Control

OTHER

normal renal function subjects (enrolled to match each End Stage Renal Disease subject) will be dosed with 400 micrograms of lofexidine HCl with 240 mL water at the same clock time as ESRD subjects.

Drug: lofexidine HCl

Interventions

lofexidine HCl DRUG

400 micrograms

Lofexidine HCl; Matched Control

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between ages of 18-75 years at enrollment with a BMI between 18 and 38 kg/m2, inclusive. Subjects with normal renal function: gender, age (±10 years), and BMI (±15%) matched to their ESRD subject.
• Male or female; however, if female: must be using contraception if of childbearing potential or must be surgically sterile; and must not be lactating.
• Subjects with ESRD must have been receiving adequate maintenance hemodialysis (at least 3 times per week) for at least 3 months before Day -1 (i.e., approximate Kt/V \>1.1 based on subject's nephrologist and Investigator); subjects with normal renal function must have a creatinine clearance (CLcr) of less than or equal to 90 mL/min as estimated by Cockcroft and Gault or, if clinically indicated, by a 24 hour urine CLcr test.
• Subjects with ESRD must be on a stable medication program, except for medications prescribed for maintenance of hemoglobin, for at least 2 weeks before Day 1.
• At screening a matched control subject is in good health based on medical history, physical exam, laboratory profile, and ECG as judged by the Investigator.
• If subject smokes, subject agrees to limit smoking while in the study to not more than 10 cigarettes per day.
• Provides written informed consent before participation in the study, and an appropriate HIPAA (Health Insurance Portability and Accountability Act) form is signed and dated.

You may not qualify if:

• The matched control subject has a history of clinically significant disease, including cardiovascular, gastrointestinal (GI), renal, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease or the ESRD subject has a history of clinically significant disease including cardiovascular, GI, hepatic, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
• Females: pregnant, breastfeeding, planning to become pregnant, or a positive pregnancy test.
• Clinically significant illness other than renal disease or known conditions associated with renal disease for ESRD subjects, within 4 weeks before Day -1.
• Use of herbal supplements within 3 weeks before Day 1.
• Received treatment of more than a single dose of CYP3A4 inducer (e.g., rifampin, barbiturates, phenytoin, glucocorticoids, St. John's Wort) within 4 weeks before Day -1.
• Received treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, diltiazem, macrolides antibiotics) within 2 weeks before Day -1.
• Currently taking any medication identified as potentially producing QTc prolongations of 10 msec or greater.
• Received an investigational medication during the last month (30 days) preceding Day -1.
• Consumes more than 7 drinks/week for women or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) or has a significant history of alcohol abuse or drug/chemical abuse within the last 1 year.
• Consumed grapefruit or grapefruit juice within 4 days before Day 1.
• Positive urine or saliva (ESRD subjects) drug screen and alcohol breathalyzer test, unless positive result is due to an approved prescribed medication (pain medication or benzodiazepine).
• Positive human immunodeficiency virus (HIV) test or tests positive for hepatitis B surface antigen.
• Known allergy or intolerance to any compound in the test product or any other closely related compound.
• Donated blood/plasma exceeding 500 mL, during the 3 month period before Day 1.
• Abnormal electrolyte values, including any including any pre-dialysis values in ESRD subjects outside of the following ranges: potassium 3.0-6.5 mmol/L; calcium 7.0-11.0 mg/dL; sodium: 120 150 mmol/L.

Sponsors & Collaborators

• USWM, LLC (dba US WorldMeds): lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Unknown Facility

Orlando, Florida, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

lofexidine

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas Marbury, MD

  OCRS

  PRINCIPAL INVESTIGATOR

• James Longstreth, PhD

  USWM, LLC (dba US WorldMeds)

  STUDY DIRECTOR

• Charles Gorodetzky, MD

  USWM, LLC (dba US WorldMeds)

  STUDY DIRECTOR

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: December 5, 2014
• First Posted: December 9, 2014
• Study Start: November 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: October 26, 2017

Record last verified: 2017-10

Locations

US (1)