Evaluation of OSU6162 Hydrochloride as an Adjunct to SSRI/SNRI Therapy in Treatment-Resistant Major Depressive Disorder: A Double-Blind, Placebo-Controlled Study

The primary objective of this study is to assess the **effect** and tolerability of adding OSU6162 to ongoing treatment with a selective serotonin reuptake inhibitor (**SSRI**) or a serotonin and norepinephrine reuptake inhibitor (**SNRI**) in patients with SSRI/SNRI-resistant **depression**. This evaluation is clinically relevant as it aims to address the challenge of treatment-resistant depression, a condition where patients do not respond adequately to standard antidepressant therapies. By investigating the potential benefits of OSU6162 as an adjunctive treatment, the study seeks to provide insights into alternative therapeutic strategies for improving patient outcomes in this difficult-to-treat population.

The clinical trial involves participants diagnosed with **depression**, specifically those with SSRI/SNRI-resistant depression. The study population includes both male and female subjects, aged between 25 and 65 years, who meet the DSM-5 criteria for major depressive disorder. Participants are required to have a symptom-free period preceding the current episode within the past two years and must not have significantly improved after treatment with specific SSRIs or SNRIs for at least six weeks. The trial does not include a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified. 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 safety of **OSU6162** as an adjunctive treatment in patients with **SSRI/SNRI-resistant depression**. This study is a **randomized, double-blind, placebo-controlled** trial, conducted in a Phase 4 setting. The trial aims to assess the effect and tolerability of adding OSU6162 to ongoing treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitor (SNRI). The trial is expected to conclude by December 31, 2026, with recruitment having commenced on April 21, 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of major depressive disorder, and lack of significant improvement with prior SSRI/SNRI treatment. The inclusion criteria also require a signed informed consent and adherence to specific contraceptive measures for participants of childbearing potential. The primary endpoint is the change from baseline in the total score of the investigator-rated Bech 6-item subscale of the Hamilton Depression Rating Scale (HDRS) at the study's endpoint.

The trial involves a maximum treatment period of 10 weeks, during which participants will receive either OSU6162 or a placebo in the form of a **coated tablet** administered orally. The maximum daily dose is 135 mg, with a total dose not exceeding 45 mg per administration. Follow-up visits will be scheduled to monitor the participants' response to the treatment and any adverse effects. The end-of-study visit will conclude the trial for each participant, assessing the overall impact of the treatment.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including withdrawal of consent, significant adverse events, or non-compliance with the study protocol. The trial is conducted under the sponsorship of Sahlgrenska University Hospital, ensuring adherence to ethical standards and regulatory requirements.

The clinical trial involves the administration of **OSU6162**, a novel investigational medication, as an adjunctive treatment for patients with selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI)-resistant depression. **OSU6162** is chemically known as **3-(3-methanesulfonyl-phenyl)-1-propyl-piperidine hydrochloride** and is provided in the form of a **coated tablet**. Each tablet contains 15 mg of the active substance. The medication is administered orally, with a maximum daily dose of 135 mg, divided into three doses of 45 mg each. The treatment period is limited to a maximum of 10 days. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The study also includes a **placebo** group to serve as a comparator for evaluating the efficacy and safety of **OSU6162**. The placebo is also formulated as a **coated tablet** and is indistinguishable from the active medication in appearance. It is administered orally with the same dosing schedule as the active treatment, ensuring blinding of both participants and investigators. The placebo contains no active pharmaceutical ingredients and is used to assess the psychological and physiological effects of the treatment regimen. Monitoring of participant compliance is conducted similarly to the active treatment group to maintain the integrity of the trial results.

The efficacy of the investigational product, **OSU6162**, in the treatment of SSRI/SNRI-resistant depression will be assessed through a double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in the total score of the investigator-rated Bech 6-item subscale of the Hamilton Depression Rating Scale (HDRS) at the endpoint. This scale is a validated tool commonly used to measure the severity of depression symptoms.