Single-Dose Pharmacokinetics and Safety of Oral Lofexidine in Hepatically-Impaired Subjects

NCT02318836 | Completed Phase 1

• 2 other identifiers: USWM-LX1-10071R01DA030916
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, parallel-group, single-dose study of lofexidine in 6 adult subjects with mild hepatic impairment (Child Pugh score of 5 6), 6 adult subjects with moderate hepatic impairment (Child Pugh score 7 9), 6 adult subjects with severe hepatic impairment (Child Pugh score 10 15), and 6 control subjects with normal hepatic function with mean age, body mass index (BMI), and gender distribution targeted to be similar to the impaired hepatic function cohorts.

Conditions

Liver Failure

Keywords

hepatic, hepatic impairment, lofexidine

Outcome Measures

Primary Outcomes (1)

• PK Profile: Cmax, Tmax, AUC, λz, CL/F, T½, CLr, CLd, Ae

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

  pre dose until 144 hours post-dose

Secondary Outcomes (5)

• Adverse events

  screening through day 7

• Clinical laboratory tests

  screening through day 7

• Vital signs

  screening through day 7

• 12-lead ECG

  screening through day 7

• Holter ECG

  pre dose through 8 hours post dose

Study Arms (4)

Normal Hepatic function

ACTIVE COMPARATOR

Drug: Lofexidine Hydrochloride (HCl) tablets

Mild Hepatic Impairment

ACTIVE COMPARATOR

(Child-Pugh score 5-6)

Drug: Lofexidine Hydrochloride (HCl) tablets

Moderate Hepatic Impairment

ACTIVE COMPARATOR

(Child-Pugh score 7-9)

Drug: Lofexidine Hydrochloride (HCl) tablets

Severe Hepatic Impairment

ACTIVE COMPARATOR

(Child-Pugh score 10-15)

Drug: Lofexidine Hydrochloride (HCl) tablets

Interventions

Lofexidine Hydrochloride (HCl) tablets DRUG

Lofexidine HCl tablets (two 200 µg tablets) will be administered orally with 240 mL room temperature tap water as a single 400 µg dose in the morning on Day 1 after a 10 hour overnight fast.

Mild Hepatic Impairment; Moderate Hepatic Impairment; Normal Hepatic function; Severe Hepatic Impairment

Eligibility Criteria

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

You may qualify if:

• Site will evaluate each subject for criteria in detail, which will include:
• Between ages of 18 to 65 years at enrollment with a BMI between 19 and 38 kg/m2, inclusive.
• Subject is eligible to enter the study if:
• Matched control subject: normal hepatic function and free from other clinically significant illnesses or disease, and medical history, physical examination, laboratory results, and other tests consistent with health, as determined by the Investigator.
• Subject with mild hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 5-6 Points (Stage A) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.
• Subject with moderate hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 7 9 Points (Stage B) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.
• Subject with severe hepatic impairment: Child-Pugh hepatic dysfunction staging system score of 10-15 Points (Stage C) and medical history, physical examination, laboratory results, and other tests consistent with their hepatic impairment, as determined by the Investigator.

You may not qualify if:

• Site will evaluate each subject for criteria in detail, which will include:
• 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 hepatically-impaired subject has a history of clinically significant disease including cardiovascular, GI, renal, pulmonary, endocrine, hematologic, vascular, immunologic, metabolic, or collagen disease.
• Abnormal cardiovascular exam at Screening, including any of the following:
• clinically significant abnormal ECG (e.g., second or third degree heart block, uncontrolled arrhythmia, QTcF (Fridericia's correction) interval \>450 msec for males and \>470 msec for females).
• heart rate \<45 bpm or symptomatic bradycardia;
• systolic blood pressure \<90 mmHg or symptomatic hypotension;
• blood pressure \>160/100 mmHg; or
• prior history of myocardial infarction.
• Significant bleeding diathesis or esophageal bleeding within the last 8 weeks.
• Evidence of hepatic function deterioration within the last 4 weeks as indicated by liver transaminases, alkaline phosphatase, and gamma-glutamyl transpeptidase or a ≥50% worsening of serum bilirubin or prothrombin time.
• History of surgical portosystemic shunt.
• Prothrombin time \>18 seconds.

Sponsors & Collaborators

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

Study Sites (1)

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Liver Failure

Interventions

lofexidine; Tablets

Condition Hierarchy (Ancestors)

Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Thomas Marbury, MD

  Orlando Clinical Research Center

  PRINCIPAL INVESTIGATOR

• James Longstreth, PhD

  USWM, LLC (dba US WorldMeds)

  STUDY DIRECTOR

• Charles Gorodetzky, MD, PhD

  USWM, LLC (dba US WorldMeds)

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: December 17, 2014
• Study Start: June 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: February 23, 2018

Record last verified: 2018-02

Locations

US (1)