Lofexidine for Inpatient Opiate Detox in Singapore

NCT01675648 | Completed Phase 4 DMC

• 1 other identifier: Lofex00428
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

In Singapore, opiate substitution medication e.g. methadone is only licensed for use with specific population. The standard treatment is one week of detoxification assisted with diazepam and symptomatic treatment followed by one week of rehabilitation. However, diazepam is highly addictive and widely abused among heroin users and pharmacologically, does not reduce the physical and psychological craving for opioids which can trigger relapse. Many opiate patients undergoing inpatient detoxification leave prematurely (i.e. PID: patient initiated discharge) because of the severity of unpleasant withdrawal symptoms. The purpose of the study is to establish an alternative medication to reduce opiate withdrawal symptoms for use in Singapore by evaluating the clinical efficacy of Lofexidine versus Diazepam in the management of the opiate withdrawal syndrome during inpatient detoxification.

Conditions

Opiate Dependent Patients Who Are Undergoing Inpatient Detoxification in Singapore

Keywords

Opiate dependent; inpatient detoxification

Outcome Measures

Primary Outcomes (1)

• To evaluate differences in OOWS (Objective Opiate Withdrawal Scale)

  on day 3 and day 4 during inpatient dotex

Secondary Outcomes (5)

• To evaluate differences in SOWS (Short Opiate Withdrawal Scale)

  on day 3 and day 4 during inpatient detox

• To evaluate differences in pupil sizes

  on days 3 and 4 of inpatient detox

• To evaluate differences in craving on the Visual Analogue Scale

  on days 3 and 4 of inpatient detox

• To evaluate differences in time to drop-out (length of stay on the ward)

  time to drop-out

• To evaluate differences in emotional/psychological symptoms

  every 3 days

Other Outcomes (1)

• To evaluate the safety of Lofexidine with opiate dependent patients undergoing inpatient detoxification in Singapore

  during 14 days of inpatient detox

Study Arms (2)

Lofexidine & Diazepam Placebo

EXPERIMENTAL

Initial Lofexidine dosage starts from 0.8mg per day, it will be gradually increased by increments of 0.4 to 0.8mg per day up to a maximum of 2.2mg daily. After 3 peak dose days, the dosage will be gradually decreased by 0.2 to 0.6mg per day till to 0.2mg of the last lofexidine dosage in Day 10. The Diazepam placebo will be administrated to the patients with the same frequency, time and number tablets of diazepam in the active comparator arm.

Drug: Lofexidine; Drug: Placebo for Diazepam

Diazepam & Lofexidine Placebo

ACTIVE COMPARATOR

The initial dosage of Diazepam is 10 mg per day on Day 1\&2, the dosage will be increased to 15 mg per day on Day 3\&4, subsequently decreased to 10mg per day on Day 5, 5mg per day on Day 6\&7, 2mg per day on Day 8\&9\&10. The Lofexidine placebo will be administrated to the patients with the same frequency, time and number tablets of lofexidine in the experimental arm.

Drug: Diazepam; Drug: Placebo for Lofexidine

Interventions

Lofexidine DRUG

Also known as: BritLofex 0.2mg

Lofexidine & Diazepam Placebo

Diazepam DRUG

Also known as: Apo-Diazepam 5mg and 2mg

Diazepam & Lofexidine Placebo

Placebo for Lofexidine DRUG

Diazepam & Lofexidine Placebo

Placebo for Diazepam DRUG

Lofexidine & Diazepam Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who meet the DSM-IV criteria for a diagnosis of opiate dependence (as diagnosed by a NAMS psychiatrist).
• Individuals are voluntarily undergoing inpatient opiate withdrawal treatment at the National Addictions Management Service (NAMS).
• Agreeable to participating in the clinical trial and will provide written consent.
• Males or females who are between the ages of 21-55 years. The lower limit of 21 years is in place because of lack of data on younger populations. The upper limit is set at 55 years as the likelihood of having co-morbid physical health problems is greater.
• Individuals who have a positive urine screen for the presence of opiates (routinely given on first visit to outpatient clinic).

You may not qualify if:

• Are investigator site personnel directly affiliated with this study and their immediate families, immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• Are currently enrolled in, or discontinued within the last 30 days from another clinical trial or medical research judged not to be scientifically or medically compatible with this study.
• A history of allergy/sensitivity to clonidine, lofexidine, imidazole derivatives (e.g. clotrimazole, antifungal) or alpha-2-adrenergic medications.
• Co-dependency on alcohol, benzodiazepines or any other drug that would require detoxification.
• A history of major physical illness (cardiovascular disease, cerebrovascular disease, renal impairment, liver disease, epilepsy, symptomatic HIV, Hepatitis B and/or C).
• Patients with major psychiatric illness (e.g. psychotic disorders, major depression).
• Patients prescribed analgesic\*(\*: Opioid analgesic and similar narcotic analgesics), antihypertensive, antiarrhythmic, or antiretroviral medication.
• Baseline BP \> 140/90 mmHg or \< 85/55mmHg, and/or baseline PR \<55beats/min.
• Significant abnormal finding from blood tests (FBC, LFT, Renal function) and ECG during screening.
• Pregnant or breast feeding.
• Patients are receiving and not willing to stop the drugs which may cause prolong QT interval and hypotension while using concomitant with Lofexidine, e.g. thioridazine, chlorpromazine, tricyclic antidepressants.

Sponsors & Collaborators

• Institute of Mental Health, Singapore: lead
• Singapore Clinical Research Institute: collaborator

Study Sites (1)

National Addictions Management Service, Institute of Mental Health, Singapore

Singapore, Singapore, 539747, Singapore

Location

Related Publications (1)

• Guo S, Manning V, Yang Y, Koh PK, Chan E, de Souza NN, Assam PN, Sultana R, Wijesinghe R, Pangjaya J, Kandasami G, Cheok C, Lee KM, Wong KE. Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore. J Subst Abuse Treat. 2018 Aug;91:1-11. doi: 10.1016/j.jsat.2018.04.012. Epub 2018 Apr 25.

  PMID: 29910009 DERIVED

MeSH Terms

Interventions

lofexidine; Diazepam

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Song Guo, Ph.D

  NAMS IMH Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant, Head of Research, NAMS IMH

Study Record Dates

• First Submitted: August 16, 2012
• First Posted: August 30, 2012
• Study Start: August 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 28, 2015

Record last verified: 2015-08

Locations

SG (1)