Tolerability and Analgesic Efficacy of Loxapine in Patients With Refractory, Chemotherapy-induced Neuropathic Pain (LOX2015PILOT)

June 30, 2022 updated by: University of Witten/Herdecke
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • NRW
      • Wuppertal, NRW, Germany, 42283
        • Helios Clinic Wuppertal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Loxapine
Loxapine dose escalation according to tolerability and analgesic efficacy
Other Names:
  • Loxapine Succinate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Loxapine dosage with the lowest incidence of events.
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number, type, and severity of (serious) adverse events ((S)AEs)
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
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
Time Frame: 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
Time Frame: 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)
Time Frame: 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 (measured by using 11-point numeric pain rating scale) in relation to treatment phase and loxapine dosage
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)
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Assessment of the association between the pattern of events (Primary endpoint) related to the individual pain level (clinically relevant pain reduction 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.
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 (painDETECT)
Time Frame: 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 (measured by painDETECT questionnaire) in relation to treatment phase and loxapine dosage
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 (painDETECT)
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Assessment of the association between the pattern of events (Primary endpoint) related to the individual changes in pain severity / characteristics measured by painDETECT questionnaire
After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Individual (study participant-related) changes in QoL (SF-12v2)
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Individual (study participant-related) changes in the quality of life (12-item Short Form Health Survey (SF-12v2)) in relation to treatment phase and loxapine dosage
After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Association between event pattern and QoL (SF-12v2)
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Assessment of the association between the pattern of events (Primary endpoint) related to the individual quality of life changes changes (12-item Short Form Health Survey (SF-12v2))
After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Individual (study participant-related) changes in anxiety and depression (HADS-D scale)
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Individual (study participant-related) changes in anxiety and depression (HADS-D scale) in relation to treatment phase and loxapine dosage
After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Association between event pattern and anxiety and depression (HADS-D scale)
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Assessment of the association between the pattern of events (Primary endpoint) related to the individual changes in anxiety and depression (HADS-D scale)
After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Association between event pattern and analgesic co-medication
Time Frame: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
Assessment of the association between the pattern of events (Primary endpoint) related to the individual changes in analgesic co-medication
After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Witten/Herdecke

Investigators

  • Study Chair: Sven Schmiedl, MD, Witten/Herdecke University
  • Principal Investigator: Sven Schmiedl, MD, Helios Clinic Wuppertal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 7, 2016

Primary Completion (Actual)

May 4, 2017

Study Completion (Actual)

May 4, 2017

Study Registration Dates

First Submitted

June 14, 2016

First Submitted That Met QC Criteria

June 28, 2016

First Posted (Estimate)

July 1, 2016

Study Record Updates

Last Update Posted (Actual)

July 1, 2022

Last Update Submitted That Met QC Criteria

June 30, 2022

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LOX_2015_PILOT
  • 2014-005440-17 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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