Efficacy and Tolerability of AP707 in Patients with Chronic Back Pain

The primary objective of this study is the evaluation of the **efficacy** of AP707 as an add-on treatment in patients with **chronic back pain**. This is clinically relevant as chronic back pain is a prevalent condition that significantly impacts quality of life and functional ability. Identifying effective add-on treatments can enhance pain management strategies and improve patient outcomes.

Secondary objectives include the evaluation of the safety and tolerability of AP707. Assessing these parameters is crucial to ensure that the treatment is not only effective but also safe for long-term use in managing chronic back pain.

The clinical trial focuses on evaluating the efficacy of AP707 as an add-on treatment for patients with **chronic back pain**. The study population includes both female and male participants aged 18 years and older, with no upper age limit specified. Participants are required to have a life expectancy of more than one year and must be experiencing moderate to severe pain, with a pain intensity greater than 5 on the Numeric Rating Scale. The trial does not involve a vulnerable population. Participants must have completed the painDETECT questionnaire with a score of 20 or more and the QUISS questionnaire with a score of 45 or less. They should have chronic back pain persisting for at least three months and must have optimized standard care pain therapy at the study entry. Additionally, participants are expected to have a good command of the German language to comprehend study-related questionnaires. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the **efficacy** and tolerability of AP707 as an add-on treatment in patients with chronic back pain. This is a randomized, double-blind, placebo-controlled trial, conducted over an estimated duration from May 1, 2023, to December 31, 2024. The trial involves two study arms: one receiving the active treatment (verum) and the other receiving a placebo. The primary endpoint is the change in pain level on the Numeric Rating Scale (NRS) between baseline and treatment week 14. Secondary endpoints include changes in pain levels at weeks 26 and 52, as well as various other measures of pain, psychological distress, and quality of life.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, pain intensity, and language proficiency. Following randomization, participants will attend follow-up visits at specified intervals, including weeks 5, 11, 14, 18, 22, 26, 30, 34, 39, 43, 47, and 52. These visits are designed to monitor changes in pain levels, assess adverse events, and evaluate the overall impact of the treatment on the participants' quality of life. The end-of-study visit will occur at week 52, marking the conclusion of the trial for each participant.

The expected length of participant involvement is approximately 52 weeks. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with study protocols. Participants are required to use reliable contraception during the study and for three months after the last dose of the study medication. The trial aims to provide comprehensive data on the potential benefits and risks of AP707 in managing chronic back pain, contributing to the broader understanding of treatment options for this condition.

The clinical trial involves the evaluation of **AP707**, an oromucosal spray suspension, as an add-on treatment for patients with chronic back pain. The active substance in AP707 is **ADEZUNAP**, classified under the ATC code N02BG10. The pharmaceutical form is an oromucosal spray, and the administration route is sublingual. The maximum daily dose is 20.83 ml, with a total maximum dose of 923.32 ml over a treatment period of 52 weeks. Participant compliance will be monitored through regular assessments.

**NAPROXEN** is included as a comparator treatment. It is administered orally in a pharmaceutical form coded as PHF00245MIG. The maximum daily dose is 1.25 grams. This non-experimental treatment serves as an analgesic reference in the study.

Another comparator is a combination of **BUCLIZINE HYDROCHLORIDE, PARACETAMOL, and CODEINE PHOSPHATE**. This combination is administered in a form coded as PHF00082MIG, with a maximum daily dose of 4000 mg. The route of administration is unspecified, categorized as "OTHER USE." This combination is used to evaluate its analgesic efficacy compared to AP707.

**DICLOFENAC** is also used as a comparator, with a pharmaceutical form coded as PHF1059MIG. The maximum daily dose is 150 mg, and the administration route is unspecified. It serves as an additional analgesic reference.

**PHENAZONE** is administered orally in a form coded as PHF00242MIG, with a maximum daily dose of 4 grams. It is included as a standard analgesic treatment in the trial.

**KETOPROFEN** is administered transdermally in a form coded as PHF00231MIG, with a maximum daily dose of 400 mg. This route of administration provides an alternative analgesic approach in the study.

**DEXIBUPROFEN** is administered orally in a form coded as PHF00170MIG, with a maximum daily dose of 1200 mg. It is included as a comparator analgesic treatment.

**ACECLOFENAC** is administered orally in a form coded as PHF00082MIG, with a maximum daily dose of 200 mg. It serves as an additional analgesic reference in the trial.

**ACEMETACIN** is administered orally in a form coded as PHF00006MIG, with a maximum daily dose of 300 mg. It is included as a standard analgesic treatment.

**TIAPROFENIC ACID** is administered orally in a form coded as PHF00245MIG, with a maximum daily dose of 600 mg. It serves as an additional analgesic reference.

**DEXKETOPROFEN** is administered via IV injection or infusion in a form coded as PHF00230MIG, with a maximum daily dose of 150 mg. This route provides an alternative analgesic approach.

**ACETYLSALICYLIC ACID** is administered orally in a form coded as PHF00169MIG, with a maximum daily dose of 3000 mg. It is included as a standard analgesic treatment.

**METAMIZOLE SODIUM** is administered in a form coded as PHF00245MIG, with a maximum daily dose of 4 grams. The route of administration is unspecified, categorized as "OTHER USE." It serves as an additional analgesic reference.

**IMIPRAMINE** is administered orally in a form coded as PHF00082MIG, with a maximum daily dose of 300 mg. It is included as an antidepressant with analgesic effects.

**CELECOXIB** is administered orally in a form coded as PHF00005MIG, with a maximum daily dose of 400 mg. It serves as an additional analgesic reference.

**AMITRIPTYLINE** is administered orally in a form coded as PHF00082MIG, with a maximum daily dose of 150 mg. It is included as a tricyclic antidepressant with analgesic effects.

A placebo is also utilized in the trial, formulated as a pump spray for sublingual application in 20 mL bottles. The placebo contains all excipients of AP707 without the active ingredient, cannabis sativa, and is characterized by a brown-beige appearance with a sweet, slightly fruity odor. This placebo is used to assess the efficacy of AP707 against a non-active control.

The efficacy of the investigational product AP707 in patients with chronic back pain will be assessed using several primary and secondary endpoints. The primary endpoint is the change in pain level on the Numeric Rating Scale (NRS, 0-10) between baseline and treatment week 14, comparing study arm 1 (verum) and study arm 2 (placebo). Secondary endpoints include changes in pain level on the NRS at treatment weeks 26 and 52, as well as changes in the pain score of the Neuropathic Pain Symptom Inventory (NPSI) questionnaire at weeks 14, 26, and 52. Additional secondary endpoints involve responder analysis for improvements in pain score, changes in pain-related impairment, psychological distress, quality of life, sleep quality, and the use of rescue medication.

Efficacy parameters will be measured at various timepoints throughout the trial, including weeks 5, 11, 14, 18, 22, 26, 30, 34, 39, 43, 47, and 52. The tools and instruments used for these assessments include the NRS, NPSI, Depression Anxiety Stress Scales Short Form (DASS-21), Veterans RAND (VR-12) questionnaire, Regensburg Insomnia Scale (RIS), and the Brief Pain Inventory - Short Form (BPI-SF). The analysis will also consider the area under the NRS-curve and the number and severity of adverse events. These assessments will provide a comprehensive evaluation of the efficacy of AP707 as an add-on treatment for chronic back pain.