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

NCT02820519 | Terminated Phase 2

• 2 other identifiers: LOX_2015_PILOT2014-005440-17
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuropathic Pain

Keywords

Neuropathic pain; Loxapine; Antipsychotics; Co-Analgesics; Tolerability; Analgesic efficacy

Outcome Measures

Primary Outcomes (1)

• Loxapine dosage with the lowest incidence of events.

  The primary endpoint is defined as the first occurrence of a (serious) adverse event ((S)AE) leading to dose reduction or withdrawal of loxapine ("event"). The loxapine dosage with the lowest incidence of events will be identified.

  After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)

Secondary Outcomes (12)

• Number, type, and severity of (serious) adverse events ((S)AEs)

  After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)

• Cumulative incidence rates for (S)AE pattern of study participants

  After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)

• Individual (study participant-related) incidence of individual (S)AEs

  After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)

• Individual (study participant-related) changes in pain severity (NRS scale)

  After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)

• Association between event pattern and individual pain level (NRS scale)

  After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)

Study Arms (1)

Loxapine

EXPERIMENTAL

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.

Drug: Loxapine

Interventions

Loxapine DRUG

Loxapine dose escalation according to tolerability and analgesic efficacy

Also known as: Loxapine Succinate

Loxapine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Witten/Herdecke: lead

Study Sites (1)

HELIOS Clinic Wuppertal

Wuppertal, North Rhine-Westphalia, 42283, Germany

Location

Related Publications (1)

• 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.

  PMID: 31402867 DERIVED

MeSH Terms

Conditions

Neuralgia

Interventions

Loxapine

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dibenzoxazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sven Schmiedl, MD

  Witten/Herdecke University

  STUDY CHAIR

• Sven Schmiedl, MD

  HELIOS Clinic Wuppertal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2016
• First Posted: July 1, 2016
• Study Start: June 7, 2016
• Primary Completion: May 4, 2017
• Study Completion: May 4, 2017
• Last Updated: July 1, 2022

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)