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

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ClinicalTrials.gov Identifier: NCT02820519
Recruitment Status : Terminated (Intolerable high amount of adverse events)
First Posted : July 1, 2016
Last Update Posted : August 28, 2017
Sponsor:
Information provided by (Responsible Party):
University of Witten/Herdecke

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.

Condition or disease Intervention/treatment Phase
Neuropathic Pain Drug: Loxapine Phase 2

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  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Tolerability and Analgesic Efficacy of Loxapine in Patients With Refractory, Chemotherapy-induced Neuropathic Pain
Study Start Date : June 2016
Actual Primary Completion Date : July 21, 2017
Actual Study Completion Date : July 21, 2017

Resource links provided by the National Library of Medicine


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 Name: Loxapine Succinate




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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))

  10. 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

  11. 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)

  12. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02820519


Locations
Germany
HELIOS Clinic Wuppertal
Wuppertal, NRW, Germany, 42283
Sponsors and Collaborators
University of Witten/Herdecke
Investigators
Study Chair: Sven Schmiedl, MD Witten/Herdecke University
Principal Investigator: Sven Schmiedl, MD HELIOS Clinic Wuppertal

Responsible Party: University of Witten/Herdecke
ClinicalTrials.gov Identifier: NCT02820519     History of Changes
Other Study ID Numbers: LOX_2015_PILOT
2014-005440-17 ( EudraCT Number )
First Posted: July 1, 2016    Key Record Dates
Last Update Posted: August 28, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University of Witten/Herdecke:
Neuropathic pain
Loxapine
Antipsychotics
Co-Analgesics
Tolerability
Analgesic efficacy

Additional relevant MeSH terms:
Neuralgia
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Analgesics
Loxapine
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action