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

Sponsor

University of Witten/Herdecke (Other)

Overall Status

Terminated

CT.gov ID

NCT02820519

Collaborator

(none)

Enrollment

Location

Arm

10.9

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

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 :

Jun 7, 2016

Actual Primary Completion Date :

May 4, 2017

Actual Study Completion Date :

May 4, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Loxapine dosage with the lowest incidence of events. [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

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)]
Number, type, and severity of (serious) adverse events ((S)AEs)
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)]
Cumulative incidence rates for (S)AE pattern of study participants
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) incidence of individual (S)AEs
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)]
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
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)]
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.
Individual (study participant-related) changes in pain severity (painDETECT) [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
Association between event pattern and individual pain level (painDETECT) [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
Individual (study participant-related) changes in QoL (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 the quality of life (12-item Short Form Health Survey (SF-12v2)) in relation to treatment phase and loxapine dosage
Association between event pattern and QoL (SF-12v2) [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))
Individual (study participant-related) 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)]
Individual (study participant-related) changes in anxiety and depression (HADS-D scale) in relation to treatment phase and loxapine dosage
Association between event pattern and anxiety and depression (HADS-D scale) [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)
Association between event pattern and analgesic co-medication [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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