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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005440-17 | EudraCT Number |
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Intolerable high amount of adverse events
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Loxapine | Drug | Loxapine dose escalation according to tolerability and analgesic efficacy |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Number, type, and severity of (serious) adverse events ((S)AEs) | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sven Schmiedl, MD | Witten/Herdecke University | Study Chair |
| Sven Schmiedl, MD | HELIOS Clinic Wuppertal | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HELIOS Clinic Wuppertal | Wuppertal | North Rhine-Westphalia | 42283 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31402867 | Derived | 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. |
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| ID | Term |
|---|---|
| D009437 | Neuralgia |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D008152 | Loxapine |
| ID | Term |
|---|---|
| D003989 | Dibenzoxazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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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 | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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 | 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) |
| D009461 |
| Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |