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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06071975
• Other study ID #: DISCOVER__(PNP1)
• Status: Recruiting
• Phase: Phase 3
• Start date: November 2, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: Apurano Pharmaceuticals GmbH
• Contact: Marko Blisse
• Phone: +49 8024 46869 28
• Email: marko.blisse[@]apurano.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 558
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Pain
• Chronic Pain Syndrome
• Diabetes
• Diabetic Neuropathies
• Diabetic Polyneuropathy
• Neuralgia
• Pain
• Pain Syndrome
• Pain, Chronic
• Peripheral Nervous System Diseases
• Peripheral Neuropathy
• Polyneuropathies
• Somatoform Disorders
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Germany	Klinikum Rechts der Isar (Zentrum für Interdisziplinäre Schmerztherapie)	Munich	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Apurano Pharmaceuticals GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number and severity of adverse events (AE)		Week 1 to 52
Primary	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	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)		Once daily in week 4 and 26
Secondary	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)		Once daily in week 4 and 52
Secondary	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)		Once in week 1, 14, 26 and 52
Secondary	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)		Several times weekly in week 4, 5, 11, 18, 22, 30, 34, 43 and 47
Secondary	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)	Week 14, 26 and 52
Secondary	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
Secondary	Change in psychological distress using Depression Anxiety Stress Scales Short Form (DASS-21) questionnaire from start to week 14, 26, and 52		Week 1, 14, 26 and 52
Secondary	Change of Patient Global Impression of Change (PGIC) from start to week 14, 26, and 52		Week 14, 26 and 52
Secondary	Change in quality of life using the Veterans RAND (VR-12) questionnaire from start to week 14, 26, and 52		Week 1, 14, 26 and 52
Secondary	Change in sleep quality using the Regensburg Insomnia Scale (RIS) from start to week 14, 26, and 52		Week 1, 14, 26 and 52
Secondary	Change in pain score of the Brief Pain Inventory - Short Form (BPI-SF) questionnaire from start to week 14, 26, and 52		Week 1, 14, 26 and 52
Secondary	Area under NRS-curve until treatment week 5, 11, 14, 18, 22, 26, 30, 34, 39, 43, 47, 52		Week 5, 12, 18, 22, 26, 30, 34, 39, 43, 47 and 52
Secondary	Change in VR-12 components (physical component summary PCS, mental component summary MCS) from start to week 14, 26, and 52		Week 1, 14, 26 and 52
Secondary	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		Week 5, 11, 14, 18, 22, 26, 30, 34, 43, 47 and 52