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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Witten/Herdecke

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 7, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 4, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 4, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 14, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 1, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 1, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LOX_2015_PILOT
  • 2014-005440-17 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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