Study to Assess Safety, Tolerability, and Interactions of Cocaine and Oral AFQ056

NCT04771143 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: CAFQ056A02101
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study to assess safety, tolerability and interactions of AFQ056 and cocaine in patients with cocaine use disorder.

Conditions

Cocaine Use Disorder

Keywords

safety; tolerability; interaction; cocaine; cocaine use disorder; AFQ056

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Treatment Emergent Adverse Events

  The distribution of adverse events (AEs) will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

  up to 26 days post-drug administration with a 30-day safety follow-up call

Secondary Outcomes (17)

• Observed maximum plasma concentration (Cmax) for cocaine and benzoylecgonine (BE)

  Day 2, Day 10

• Area Under the plasma concentration-time Curve from the time 0 to the last observed quantifiable concentration (AUC(0-t)) for cocaine and benzoylecgonine (BE)

  Day 2, Day 10

• Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) for cocaine and benzoylecgonine (BE)

  Day 2, Day 10

• Time of maximum observed drug concentration occurrence (Tmax) for cocaine and benzoylecgonine (BE)

  Day 2, Day 10

• Terminal rate constant (λz) for cocaine and benzoylecgonine (BE)

  Day 2, Day 10

Study Arms (2)

AFQ056

EXPERIMENTAL

Experimental study drug

Drug: AFQ056

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

AFQ056 DRUG

oral administration

AFQ056

Placebo DRUG

matching placebo for oral administration

Placebo

Eligibility Criteria

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

You may qualify if:

• Non-treatment seeking participants who meet DSM-V criteria for cocaine use disorder as assessed using the Mini International Neuropsychiatric Interview (MINI) neuropsychiatric interview (version 7.0).
• Be between 18 and 55 years of age, inclusive
• Have a body mass index (BMI) within a range of 18.0 to 34.0 kg/m2 and a minimum weight of at least 50.0 kg at screening.
• Have experience using cocaine by the smoked or IV route at least 6 times in the past 12 months prior to clinic intake (Day -3) and at least one use within the past 30 days.
• Provide a urine sample positive for cocaine at least once during screening (Days -28 to -4).

You may not qualify if:

• Have a current or past history of seizure disorder, including alcohol- or stimulant-related seizure, febrile seizure, or significant family history of idiopathic seizure disorder.
• Have any previous medically adverse reaction to cocaine, including loss of consciousness, chest pain, paranoid reaction or seizure.
• Have clinically significant findings in the opinion of an investigator based on the MINI (version 7.0) neuropsychiatric interview.
• Be pregnant or lactating.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception from at least 30 days prior to the first administration of study treatment (Day -2), while taking study treatment, and for at least 30 days after the last dose of the study treatment.
• Have a systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg and heart rate \> 100 beats per minute at screening or clinic intake (Day -3).
• Have a history of liver or renal disease or current elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or creatinine, 1.5 × the upper limit of normal at screening or intake (Day -3).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• National Institute on Drug Abuse (NIDA): collaborator

MeSH Terms

Interventions

mavoglurant

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a participant- and investigator-blinded study. Site staff may be unblinded to the treatment assignment of one or more participants if deemed appropriate to aid decision-making. Drug product will be supplied in bulk, so an unblinded pharmacy team who is independent of the study team will be required in order to maintain the blind. The following unblinded roles are required for this study: * Unblinded field monitor(s) * Unblinded sample analyst(s)
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will undergo a screening infusion session with saline and cocaine on Day -2 as part of the eligibility determination. Once deemed eligible, participants will undergo screening infusion sessions 2 and 3 on Days 1 and 2 respectively. Starting Day 3, participants will receive either AFQ056 or matching placebo twice a day from Day 3 to Day 9. The AFQ056 treatment group will be up titrated to 200 mg according to the following dosing schedule: Day 3: 50 mg twice daily; Day 4: 100 mg twice daily and Days 5-9: 200 mg twice daily. On Day 10, participants will be administered only the morning dose of AFQ056 200 mg or placebo. On Days 9 and 10, participants will have infusion session 4 and 5 respectively. The participants will be discharged from the clinic on Day 12 and return for a follow-up visit between 7 to 14 days after clinic discharge. A safety follow-up call will be conducted on Day 40.

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: February 25, 2021
• Study Start: July 21, 2021
• Primary Completion: January 3, 2022
• Study Completion: January 3, 2022
• Last Updated: July 1, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share