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

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 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.

Study Overview

• Status: Recruiting
• Conditions: Pain; Diabetes; Diabetic Neuropathies; Chronic Pain; Peripheral Neuropathy; Pain, Chronic; Chronic Pain Syndrome; Diabetic Polyneuropathy; Pain Syndrome; Peripheral Neuralgia; Peripheral Neuropathy With Type 2 Diabetis
• Intervention / Treatment: Drug: Adezunap (AP707); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 558
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marko Blisse; Phone Number: +49 8024 46869 28; Email: marko.blisse@apurano.de

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • Klinikum Rechts der Isar (Zentrum für Interdisziplinäre Schmerztherapie)
      • Contact: Katharina Haas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed and dated informed consent form
2. Patients with chronic pain due to diabetic polyneuropathy since at least 3 months
3. Female and male patients (> 18 years)
4. Patients with more than 1 year life expectancy
5. Patients with optimized sCPT on study entry as defined in section 3.1.1 and section 3.1.3 of the study protocol
6. Willingness of study patients of both sexes to use reliable contraception during study participation and for three months after taking the last study medication
7. Good command of German language, in order to understand questionnaires in German
8. 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
9. Completed QUISS (Quantification Inventory for Somatoform Syndromes) questionnaire with 45 or less score points

Exclusion Criteria:

1. Medical history of hypersensitivity or intolerance to the investigational product or its ingredients or to ingredients of similar chemical structure
2. Known intolerance to cannabinoids or cannabis products.
3. Participation in another clinical trial within the last four weeks prior to inclusion.
4. Pregnant or nursing women (as excluded by pregnancy testing at visit 1).
5. Other medical conditions that do not allow the trial subject to appraise the nature, scope, and potential consequences of the clinical trial
6. Indications that the trial subject is unlikely to comply with the study protocol (e.g., unwillingness to cooperate)
7. Known use of medicinal cannabis products within the last 8 weeks
8. Active malignant tumor disease, tumor pain, or other dominant severe pain other than that of the study indication
9. Known history of severe liver or kidney diseases
10. Known history of severe cardiovascular disease
11. Known history of or acute mental illness such as severe depression, psychosis, bipolar disorder, mania, anxiety, or obsessive-compulsive disorder
12. Known history of addictive disease (e.g., alcohol, medication, drug addiction)
13. Answered during Screening less than 12 times of 18 the pain intensity (NRS) inquiry
14. 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
15. Laboratory renal value: Serum creatinine > 1.5 ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.	Drug: Adezunap (AP707); Sublingual spray with maximum application of 16 actuations per day or a maximum daily dose of 17,6mg THC distributed over 4 daily intakes.
Placebo Comparator: Control group; Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.	Drug: Placebo; Sublingual spray with maximum application of 16 actuations per day distributed over 4 daily intakes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)	Once daily in Week 4 and 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		Week 14
Change in the pain score of the Neuropathic Pain Symptom Inventory (NPSI) questionnaire between baseline and at treatment week 14 in comparison of study arm 1 (verum) and study arm 2 (placebo)		Week 1 and 14
Change in pain level on the Numeric Rating Scale (0-10) between baseline and in treatment week 5 and 11 in comparison of study arm 1 (verum) and study arm 2 (placebo)		Several times weekly in week 4, 5 and 11
Responder analysis for endpoints 1) for treatment week 14	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)	Week 14
Change in psychological distress using Depression Anxiety Stress Scales Short Form (DASS-21) questionnaire from start to week 14		Week 1 and 14
Change of Patient Global Impression of Change (PGIC) from start to week 14		Week 14
Change in quality of life using the Veterans RAND (VR-12) questionnaire from start to week 14		Week 1 and 14
Change in sleep quality using the Regensburg Insomnia Scale (RIS) from start to week 14		Week 1 and 14
Change in pain score of the Brief Pain Inventory - Short Form (BPI-SF) questionnaire from start to week 14		Week 1 and 14
Area under NRS-curve until treatment week 5, 11 and 14		Week 5, 11 and 14
Change in VR-12 components (physical component summary PCS, mental component summary MCS) from start to week 14		Week 1 and 14
Number of patients with rescue medication over the course of the clinical trial and within periods: until treatment week ≤5, ≤11 and ≤14		Week 5, 11 and 14

Other Outcome Measures

Outcome Measure	Time Frame
Number and severity of adverse events (AE)	Week 1 to 14

Collaborators and Investigators

• Sponsor: Apurano Pharmaceuticals GmbH

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 25, 2023
• First Submitted That Met QC Criteria: October 5, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Chronic Pain; Cannabis; THC; Peripheral Neuropathy; Diabetic Polyneuropathy; Tetrahydrocannabinol; Cannabinoids; Diabetic Neuropathies; Pain Syndrome; Pain Therapy; Diabetis; Chronic Pain Syndrome; Adezunap; Peripheral Neuralgia; Peripheral Neuropathy with Type 2 Diabetis; Delta-9-Tetrahydrocannabinol
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Pain; Neurologic Manifestations; Endocrine System Diseases; Disease; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Syndrome; Chronic Pain; Neuralgia; Peripheral Nervous System Diseases; Somatoform Disorders; Polyneuropathies; Diabetic Neuropathies
• Other Study ID Numbers: DISCOVER_(PNP1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No