Tolerability and Analgesic Efficacy of Loxapine in Patients With Refractory, Chemotherapy-induced Neuropathic Pain

NCT ID: NCT02820519

Last Updated: 2022-07-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-07
• Study Completion Date: 2017-05-04

Brief Summary

Loxapine is an antipsychotic drug approved for the treatment of schizophrenia in several countries including the United States. In animal studies in mice, loxapine reduced neuropathic pain. Hence, in a proof-of-principle and dose-escalating study the tolerability and analgesic efficacy of loxapine will be evaluated in patients with neuropathic pain.

Detailed Description

In this dose-escalating study, 12 patients with refractory, chemotherapy-induced neuropathic pain (including mixed pain) will receive loxapine during four 14-days treatment episodes. The dosage for episode 1 (Days 1-14) will be 10 mg b.i.d., dosages for episodes 2, 3, and 4 will be defined by taking into account tolerability and analgesic efficacy of the former episode. In case of an acceptable tolerability and if a clinically relevant analgesic efficacy is not reached, loxapine dosage will be increased (2nd Episode 10 mg t.i.d, 3rd Episode 20 mg b.i.d., 4th episode 20 mg t.i.d.). In case of an acceptable tolerability and if a clinically relevant analgesic efficacy is reached, loxapine dosage will not be changed. If clinically relevant (serious) adverse events ((S)AEs) occur, loxapine dosage will be reduced or the treatment will be interrupted or stopped irrespective of the analgesic efficacy. A clinically relevant pain reduction / analgesic efficacy is defined by an at least 30% decrease or an absolute decrease of two scale units compared to baseline using 11-point numeric pain rating scale. Patients will receive loxapine as add-on treatment to their usual (analgesic) care.

Conditions

Neuropathic Pain

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Loxapine

Loxapine Capsules 10 mg Day 1- 14: 10 mg b.i.d Day 15-28: 10 mg t.i.d Day 29-42: 20 mg b.i.d. Day 43-56: 20 mg t.i.d. Dosages will be escalated according to analgesic efficacy and tolerability.

Group Type: EXPERIMENTAL

Loxapine

Intervention Type: DRUG

Loxapine dose escalation according to tolerability and analgesic efficacy

Interventions

Loxapine

Loxapine dose escalation according to tolerability and analgesic efficacy

Intervention Type: DRUG

Other Intervention Names

Loxapine Succinate

Eligibility Criteria

Inclusion Criteria

• Primarily chemotherapy-induced neuropathic pain (including mixed pain) for at least 3 months refractory to at least one analgesic compound
• Neuropathic pain >= 4 (11-point numeric pain scale) at screening visit (including mixed pain)
• Age >= 18 years
• Body weight between 50 and 150 kg
• Given written informed consent

Exclusion Criteria

• Participation in other interventional clinical studies (currently or within the last 3 months)
• Parkinson's disease, movement disorders (extrapyramidal signs and symptoms) associated with antipsychotics, neuroleptic malignant syndrome, other syndromes associated with antipsychotics
• Severe hypotension with a syncope in history, glaucoma, urinary retention, epilepsy or other seizure disorders in history, severe dementia, dementia-related psychosis in history, malignancies with a life expectancy of less than 6 months, breast cancer in history, other life-threatening conditions
• Corrected QT interval (QTc) > 460 ms (females) or > 450 ms (males)
• Known alcohol and/or drug abuse
• Concomitant intake of antipsychotics, dopamine agonists (Levodopa, bromocriptine, lisuride, pergolide, ropinirole, cabergoline, pramipexole, apomorphine), alpha-receptor blocking compounds
• Compounds with a strong evidence for a clinically relevant QT interval prolongation or torsade de pointes risk increase
• Strong inhibitors of CYP1A2, CYP2D6, or CYP3A4
• Known CYP2D6 Poor metabolizer status
• Pregnancy or lactation period
• Missing or insufficient contraception in pre- or perimenopausal women
• Close Affiliation with the investigational site

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Witten/Herdecke

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sven Schmiedl, MD

Role: STUDY_CHAIR

Witten/Herdecke University

Sven Schmiedl, MD

Role: PRINCIPAL_INVESTIGATOR

HELIOS Clinic Wuppertal

Locations

HELIOS Clinic Wuppertal

Wuppertal, North Rhine-Westphalia, Germany

Countries

Germany

References

Schmiedl S, Peters D, Schmalz O, Mielke A, Rossmanith T, Diop S, Piefke M, Thurmann P, Schmidtko A. Loxapine for Treatment of Patients With Refractory, Chemotherapy-Induced Neuropathic Pain: A Prematurely Terminated Pilot Study Showing Efficacy But Limited Tolerability. Front Pharmacol. 2019 Jul 25;10:838. doi: 10.3389/fphar.2019.00838. eCollection 2019.

Reference Type: DERIVED

PMID: 31402867 (View on PubMed)

Other Identifiers

2014-005440-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LOX_2015_PILOT

Identifier Type: -

Identifier Source: org_study_id