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Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy

Primary Purpose

Pain, Pain Syndrome, Pain, Chronic

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Adezunap (AP707)
Placebo
Sponsored by
Apurano Pharmaceuticals GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain focused on measuring Adezunap, Pain Therapy, Pain, Pain Syndrome, Chronic Pain, Chronic Pain Syndrome, Diabetis, Diabetic Neuropathies, Diabetic Polyneuropathy, Peripheral Neuralgia, Peripheral Neuropathy, Peripheral Neuropathy with Type 2 Diabetis, THC, Tetrahydrocannabinol, Delta-9-Tetrahydrocannabinol, Cannabis, Cannabinoids

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed and dated informed consent form Patients with chronic pain due to diabetic polyneuropathy since at least 3 months Female and male patients (> 18 years) Patients with more than 1 year life expectancy Patients with optimized sCPT on study entry as defined in section 3.1.1 and section 3.1.3 of the study protocol Willingness of study patients of both sexes to use reliable contraception during study participation and for three months after taking the last study medication Good command of German language, in order to understand questionnaires in German Current moderate to severe pain with pain intensity > 5 on Numeric Rating Scale (NRS, 0 - 10) and thus an existing need for further pain therapy Completed QUISS (Quantification Inventory for Somatoform Syndromes) questionnaire with 45 or less score points Exclusion Criteria: Medical history of hypersensitivity or intolerance to the investigational product or its ingredients or to ingredients of similar chemical structure Known intolerance to cannabinoids or cannabis products. Participation in another clinical trial within the last four weeks prior to inclusion. Pregnant or nursing women (as excluded by pregnancy testing at visit 1). Other medical conditions that do not allow the trial subject to appraise the nature, scope, and potential consequences of the clinical trial Indications that the trial subject is unlikely to comply with the study protocol (e.g., unwillingness to cooperate) Known use of medicinal cannabis products within the last 8 weeks Active malignant tumor disease, tumor pain, or other dominant severe pain other than that of the study indication Known history of severe liver or kidney diseases Known history of severe cardiovascular disease Known history of or acute mental illness such as severe depression, psychosis, bipolar disorder, mania, anxiety, or obsessive-compulsive disorder Known history of addictive disease (e.g., alcohol, medication, drug addiction) Answered during Screening less than 12 times of 18 the pain intensity (NRS) inquiry Laboratory liver values: Alanine aminotransferase (ALT, GPT) > 3 x ULN (Upper Limit of Normal range), Aspartate aminotransferase (AST, GOT) > 3 x ULN, Alkaline phosphatase (AP) > 2.5 x ULN, and for bilirubin > 1.5 x ULN Laboratory renal value: Serum creatinine > 1.5 ULN

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Treatment group

    Control group

    Arm Description

    Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.

    Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.

    Outcomes

    Primary Outcome Measures

    Change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and at treatment week 14 (end of first treatment phase) in comparison of study arm 1 (verum) and study arm 2 (placebo)

    Secondary Outcome Measures

    Change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and at treatment week 26 (end of second treatment phase) in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and at treatment week 52 (end of third treatment phase) in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Change in the pain score of the Neuropathic Pain Symptom Inventory (NPSI) questionnaire between baseline and at treatment week 14, treatment week 26 and treatment week 52 in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Change in pain level on the Numeric Rating Scale (0-10) between baseline and in treatment week 5, 11, 18, 22, 30, 34, 43, 47 in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Responder analysis for endpoints 1), 2), 3) and 4) for treatment week 14, 26 and 52
    Proportion of patients who experienced > 30 % improvement in pain score (Numeric Rating Scale) Proportion of patients who experienced > 40 % improvement in pain score (Numeric Rating Scale) Proportion of patients who experienced > 50 % improvement in pain score (Numeric Rating Scale)
    Change in sCPT (percentage of change in dosage and percentage of change in combination of analgesic measures) in both study arms from start to week 14
    Change in psychological distress using Depression Anxiety Stress Scales Short Form (DASS-21) questionnaire from start to week 14, 26, and 52
    Change of Patient Global Impression of Change (PGIC) from start to week 14, 26, and 52
    Change in quality of life using the Veterans RAND (VR-12) questionnaire from start to week 14, 26, and 52
    Change in sleep quality using the Regensburg Insomnia Scale (RIS) from start to week 14, 26, and 52
    Change in pain score of the Brief Pain Inventory - Short Form (BPI-SF) questionnaire from start to week 14, 26, and 52
    Area under NRS-curve until treatment week 5, 11, 14, 18, 22, 26, 30, 34, 39, 43, 47, 52
    Change in VR-12 components (physical component summary PCS, mental component summary MCS) from start to week 14, 26, and 52
    Number of patients with rescue medication over the course of the clinical trial and within periods: until treatment week ≤5, ≤11, ≤14, ≤18, ≤22, ≤26, ≤30, ≤34, ≤43, ≤47, ≤52

    Full Information

    First Posted
    September 25, 2023
    Last Updated
    October 5, 2023
    Sponsor
    Apurano Pharmaceuticals GmbH
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06071975
    Brief Title
    Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
    Official Title
    Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 15, 2023 (Anticipated)
    Primary Completion Date
    September 30, 2024 (Anticipated)
    Study Completion Date
    December 31, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Apurano Pharmaceuticals GmbH

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Over the last years a rising medical need for treatment of chronic pain was identified. Based on previous findings indicating the pain modulating effects of cannabinoids in chronic pain disorders, this clinical trial investigates the long term efficacy and tolerability of the THC-focused nano endocannabinoid system modulator AP707 in patients with pain disorders due to diabetic polyneuropathy. Patients receive AP707 or placebo over the course of 14 weeks as an add-on to the standard of care. Changes in pain intensity, quality of life and sleep and others measures are monitored through different scales to assess the efficacy of AP707 in patients with chronic pain due to diabetic polyneuropathy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pain, Pain Syndrome, Pain, Chronic, Chronic Pain, Chronic Pain Syndrome, Diabetes, Diabetic Neuropathies, Diabetic Polyneuropathy, Peripheral Neuralgia, Peripheral Neuropathy, Peripheral Neuropathy With Type 2 Diabetis
    Keywords
    Adezunap, Pain Therapy, Pain, Pain Syndrome, Chronic Pain, Chronic Pain Syndrome, Diabetis, Diabetic Neuropathies, Diabetic Polyneuropathy, Peripheral Neuralgia, Peripheral Neuropathy, Peripheral Neuropathy with Type 2 Diabetis, THC, Tetrahydrocannabinol, Delta-9-Tetrahydrocannabinol, Cannabis, Cannabinoids

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    558 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment group
    Arm Type
    Experimental
    Arm Description
    Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.
    Arm Title
    Control group
    Arm Type
    Experimental
    Arm Description
    Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.
    Intervention Type
    Drug
    Intervention Name(s)
    Adezunap (AP707)
    Intervention Description
    Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.
    Primary Outcome Measure Information:
    Title
    Change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and at treatment week 14 (end of first treatment phase) in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Time Frame
    Once daily in week 4 and 14
    Secondary Outcome Measure Information:
    Title
    Change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and at treatment week 26 (end of second treatment phase) in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Time Frame
    Once daily in week 4 and 26
    Title
    Change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and at treatment week 52 (end of third treatment phase) in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Time Frame
    Once daily in week 4 and 52
    Title
    Change in the pain score of the Neuropathic Pain Symptom Inventory (NPSI) questionnaire between baseline and at treatment week 14, treatment week 26 and treatment week 52 in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Time Frame
    Once in week 1, 14, 26 and 52
    Title
    Change in pain level on the Numeric Rating Scale (0-10) between baseline and in treatment week 5, 11, 18, 22, 30, 34, 43, 47 in comparison of study arm 1 (verum) and study arm 2 (placebo)
    Time Frame
    Several times weekly in week 4, 5, 11, 18, 22, 30, 34, 43 and 47
    Title
    Responder analysis for endpoints 1), 2), 3) and 4) for treatment week 14, 26 and 52
    Description
    Proportion of patients who experienced > 30 % improvement in pain score (Numeric Rating Scale) Proportion of patients who experienced > 40 % improvement in pain score (Numeric Rating Scale) Proportion of patients who experienced > 50 % improvement in pain score (Numeric Rating Scale)
    Time Frame
    Week 14, 26 and 52
    Title
    Change in sCPT (percentage of change in dosage and percentage of change in combination of analgesic measures) in both study arms from start to week 14
    Time Frame
    Week 14
    Title
    Change in psychological distress using Depression Anxiety Stress Scales Short Form (DASS-21) questionnaire from start to week 14, 26, and 52
    Time Frame
    Week 1, 14, 26 and 52
    Title
    Change of Patient Global Impression of Change (PGIC) from start to week 14, 26, and 52
    Time Frame
    Week 14, 26 and 52
    Title
    Change in quality of life using the Veterans RAND (VR-12) questionnaire from start to week 14, 26, and 52
    Time Frame
    Week 1, 14, 26 and 52
    Title
    Change in sleep quality using the Regensburg Insomnia Scale (RIS) from start to week 14, 26, and 52
    Time Frame
    Week 1, 14, 26 and 52
    Title
    Change in pain score of the Brief Pain Inventory - Short Form (BPI-SF) questionnaire from start to week 14, 26, and 52
    Time Frame
    Week 1, 14, 26 and 52
    Title
    Area under NRS-curve until treatment week 5, 11, 14, 18, 22, 26, 30, 34, 39, 43, 47, 52
    Time Frame
    Week 5, 12, 18, 22, 26, 30, 34, 39, 43, 47 and 52
    Title
    Change in VR-12 components (physical component summary PCS, mental component summary MCS) from start to week 14, 26, and 52
    Time Frame
    Week 1, 14, 26 and 52
    Title
    Number of patients with rescue medication over the course of the clinical trial and within periods: until treatment week ≤5, ≤11, ≤14, ≤18, ≤22, ≤26, ≤30, ≤34, ≤43, ≤47, ≤52
    Time Frame
    Week 5, 11, 14, 18, 22, 26, 30, 34, 43, 47 and 52
    Other Pre-specified Outcome Measures:
    Title
    Number and severity of adverse events (AE)
    Time Frame
    Week 1 to 52

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Signed and dated informed consent form Patients with chronic pain due to diabetic polyneuropathy since at least 3 months Female and male patients (> 18 years) Patients with more than 1 year life expectancy Patients with optimized sCPT on study entry as defined in section 3.1.1 and section 3.1.3 of the study protocol Willingness of study patients of both sexes to use reliable contraception during study participation and for three months after taking the last study medication Good command of German language, in order to understand questionnaires in German Current moderate to severe pain with pain intensity > 5 on Numeric Rating Scale (NRS, 0 - 10) and thus an existing need for further pain therapy Completed QUISS (Quantification Inventory for Somatoform Syndromes) questionnaire with 45 or less score points Exclusion Criteria: Medical history of hypersensitivity or intolerance to the investigational product or its ingredients or to ingredients of similar chemical structure Known intolerance to cannabinoids or cannabis products. Participation in another clinical trial within the last four weeks prior to inclusion. Pregnant or nursing women (as excluded by pregnancy testing at visit 1). Other medical conditions that do not allow the trial subject to appraise the nature, scope, and potential consequences of the clinical trial Indications that the trial subject is unlikely to comply with the study protocol (e.g., unwillingness to cooperate) Known use of medicinal cannabis products within the last 8 weeks Active malignant tumor disease, tumor pain, or other dominant severe pain other than that of the study indication Known history of severe liver or kidney diseases Known history of severe cardiovascular disease Known history of or acute mental illness such as severe depression, psychosis, bipolar disorder, mania, anxiety, or obsessive-compulsive disorder Known history of addictive disease (e.g., alcohol, medication, drug addiction) Answered during Screening less than 12 times of 18 the pain intensity (NRS) inquiry Laboratory liver values: Alanine aminotransferase (ALT, GPT) > 3 x ULN (Upper Limit of Normal range), Aspartate aminotransferase (AST, GOT) > 3 x ULN, Alkaline phosphatase (AP) > 2.5 x ULN, and for bilirubin > 1.5 x ULN Laboratory renal value: Serum creatinine > 1.5 ULN
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Marko Blisse
    Phone
    +49 8024 46869 28
    Email
    marko.blisse@apurano.de

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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