Study to Investigate Whether AFQ056 Reduces Cocaine Use in Patients Diagnosed With Cocaine Use Disorder (CUD)

A Randomized, Subject and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate Whether AFQ056 Reduces Cocaine Use in Patients Diagnosed With Cocaine Use Disorder (CUD)

This study assessed whether AFQ056 had a beneficial effect by reducing cocaine use in Cocaine Use Disorder (CUD) patients as assessed by Timeline Follow-Back cocaine self-report.

Study Overview

• Status: Completed
• Conditions: Cocaine-related Disorder
• Intervention / Treatment: Drug: Placebo; Drug: AFQ056

Detailed Description

This was a randomized, subject- and Investigator-blinded, parallel-group, placebo-controlled study in subjects with CUD. The study consisted of a 17-day screening period followed by a 12-day baseline, a 98-day outpatient treatment period (14-day up-titration dose regimen followed by 84-day maintenance dose), and an End of Study evaluation visit approximately 14 days after the last study drug administration. The total duration for each subject in the study was approximately 20 weeks including screening and baseline.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1058
    • Novartis Investigative Site
  • Buenos Aires, Argentina, 4634
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1405B0A
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08036
    • Novartis Investigative Site
  • Alicante
    • San Juan de Alicante, Alicante, Spain, 03550
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4025
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8001
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Understand the study procedures and provide written informed consent before any assessment is performed.
• Subjects diagnosed with Cocaine Use Disorder according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Ed.).
• Must use cocaine through snorting (intranasally) as primary route of administration.
• Recent cocaine use confirmed by positive urine screen for 1 or more benzoylecgonine (BE).
• Must be seeking treatment for cocaine dependence and have a desire to reduce or cease cocaine use.

Exclusion Criteria:

• Has current diagnosis of Substance Use Disorder (according to the DSM 5) on alcohol, cannabis or other stimulants, except cocaine.
• Meets current or lifetime DSM 5 criteria for schizophrenia or any psychotic disorder, or organic mental disorder.
• Have current treatment for Substance Use Disorder (e.g.: disulfiram, acamprosate, methyl phenidate, modafinil, topiramate, immediate release dexamfetamine,or baclofen).
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
• Have a history of any illness, condition, and use of medications that in the opinion of the investigator or designee might confound the results of the study or pose additional risk in administering the investigational agents to the subject or preclude successful completion of the study
• Current or/and previous treatment with concomitant medications that are strong or moderate inducers/inhibitors of CYP3A4 (e.g., clarithromycin, ketoconazole, ritonavir, etc.)
• History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
• Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the CSSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.
• Controlled hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching tablet of placebo taken orally BID	Drug: Placebo; Matching placebo tablets taken orally BID
Experimental: AFQ056; Mavoglurant was up titrated on a bid regimen followed by fixed-dose bid regimen: 50 mg bid from Day 1 to Day 7, 100 mg bid from Day 8 to Day 14, and then fixed-dose 200 mg bid for 84 days	Drug: AFQ056; 50 mg and 100 mg tablets taken orally; Other Names: mavoglurant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Cocaine Use Days	The cocaine consumption was recorded once daily (Yes/No) by the subject using the Timeline Follow-Back (TLFB) cocaine assessment tool during the treatment period. For each patient, the proportion of cocaine use days was calculated by dividing the number of days of cocaine use during the treatment period, i.e. 98 days for completers and number of days between Day 1 and day of last dose in case of premature discontinuation of study treatment.	Day 1 up to day 98

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Positive Urine Measurements of Benzoylecgonine (BE)	Urine samples were analyzed for the presence of cocaine's metabolite benzoylecgonine (BE) which is the main metabolite of cocaine present in urine. Two urine samples were provided per week to provide a quantitative measure.	Day 1 up to day 98
Proportion of Days of Alcohol Consumption	Alcohol consumption was recorded by the subjects using the Timeline Follow-Back (TLFB) alcohol self report. The number of standard drinks were recorded daily. The proportion of days of alcohol consumption during the study treatment period was was compared using an ANCOVA model with treatment as factor and past alcohol consumption as covariate. The past consumption of alcohol was the proportion of alcohol over the 28 days preceding the screening visit, which was assessed retrospectively using the TLFB.	Day 1 up to day 98
AFQ056 Plasma Concentrations	Plasma samples were collected to assess pharmacokinetics (PK)	Day 15 (0h, 2h), Day 29 (0, 2h), Day 57 (0h, 2h), Day 98 (0h,2h)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2017
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): December 16, 2019

Study Registration Dates

• First Submitted: August 4, 2017
• First Submitted That Met QC Criteria: August 4, 2017
• First Posted (Actual): August 8, 2017

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Cocaine Use Disorder; cocaine dependence,AFQ056,adult, cocaine use,CUD, drug abuse, drug addiction,
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Cocaine-Related Disorders
• Other Study ID Numbers: CAFQ056X2201; 2017-000736-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to to respect the privacy of patients who have participated in the trail in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalsutdydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No