Evaluation of Pramipexole Dihydrochloride Monohydrate in Treatment-Resistant Obsessive-Compulsive Disorder: A Randomized Controlled Pilot Study

The primary objective of this clinical trial is to evaluate the **effectiveness** of using pramipexole as an adjunctive treatment to selective serotonin reuptake inhibitors (SSRIs) in three different doses for patients with resistant **obsessive-compulsive disorder (OCD)**. This is clinically relevant as it aims to address the therapeutic challenges faced by individuals with OCD who do not respond adequately to standard SSRI treatment, potentially offering a new strategy to enhance treatment outcomes.

Secondary objectives include:

• Evaluating the **safety** of pramipexole in the treatment of resistant OCD, which is crucial for determining the risk-benefit profile of this therapeutic approach.
• Studying the biochemical, neurobiological, and psychometric changes in individuals with resistant OCD, which may provide insights into the underlying mechanisms of the disorder and the effects of pramipexole treatment.

The clinical trial focuses on evaluating the effectiveness of **pramipexole** as an augmentation strategy for selective serotonin reuptake inhibitors (SSRIs) in the treatment of resistant **obsessive-compulsive disorder (OCD)**. The study population includes both male and female participants aged between 18 and 64 years, who are diagnosed with OCD according to DSM-5 and/or ICD-10 criteria. Participants must have demonstrated resistance to first-line treatments for OCD, as evidenced by a lack of response to pharmacological treatment with at least two SSRIs at the maximum tolerated therapeutic dose for a minimum of 12 weeks, or a lack of response to augmentation with risperidone or aripiprazole for at least 6 to 12 weeks. The trial does not involve a vulnerable population, and participants are required to have European Portuguese as their mother tongue. The sponsor has not provided information regarding the total number of participants. Participants of childbearing potential must consistently and correctly use one of the specified contraceptive methods. The selection criteria ensure that the study population is well-defined and appropriate for assessing the trial's objectives.

The clinical trial is designed to evaluate the **safety** and **efficacy** of **pramipexole** treatment in patients with resistant **obsessive-compulsive disorder (OCD)**. This is a pilot, randomized, and controlled trial, which will assess the effectiveness of pramipexole as an augmentation strategy for selective serotonin reuptake inhibitors (SSRIs) in three different doses. The trial is structured as a double-blind study to ensure unbiased results. The estimated duration of the trial is from March 2024 to December 2028, with participant involvement expected to last up to 24 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, language proficiency, and resistance to previous OCD treatments. Following the screening, eligible participants will be randomized into different treatment groups receiving varying doses of pramipexole. The primary endpoint is the difference in the total score of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) between baseline and week 16. Secondary endpoints include the number of adverse events observed throughout the study duration.

Study visits will occur at regular intervals, with follow-up visits scheduled to monitor the participants' response to the treatment and any adverse events. The end-of-study visit will take place at week 24, marking the conclusion of the participant's involvement. Conditions that may lead to early termination from the study include significant adverse reactions or non-compliance with the study protocol. The trial aims to provide valuable insights into the potential of pramipexole as a treatment option for patients with resistant OCD.

The clinical trial involves the administration of **Pramipexole Aurobindo 0.35 mg tablets**. This experimental medication contains the active substance **pramipexole dihydrochloride monohydrate**. The pharmaceutical form is a tablet, and the route of administration is oral. The maximum daily dose is 0.35 mg, with a total treatment period of 14 days. The medication is manufactured by Aurobindo Pharma (Malta) Limited and is classified under the ATC code N04BC05. The active substance is of chemical origin.

Another experimental treatment in the trial is **Pramipexol Aurobindo 0.088 mg tablets**. This formulation also contains **pramipexole dihydrochloride monohydrate** as the active ingredient. The tablets are administered orally, with a maximum daily dose of 0.09 mg. The treatment duration for this dosage is 16 days. The product is produced by Puren Pharma GmbH & Co. KG and shares the same ATC classification as the other pramipexole formulations in the study.

The third experimental medication is **Pramipexol Aurobindo 0.18 mg tablets**, containing the same active substance, **pramipexole dihydrochloride monohydrate**. These tablets are also administered orally, with a maximum daily dose of 0.18 mg over a treatment period of 15 days. This product is manufactured by Aurobindo Pharma (Malta) Limited and is similarly classified under the ATC code N04BC05. All active substances in the trial are of chemical origin.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed treatment regimen.

The efficacy of pramipexole in the treatment of resistant **Obsessive-Compulsive Disorder (OCD)** will be assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The primary endpoint is the difference in the total Y-BOCS score between baseline (V1; before intervention with the investigational drug) and week 16 (V9; after intervention with the investigational drug) across different groups treated with varying doses of pramipexole. This scale is a validated tool commonly used to measure the severity of OCD symptoms, providing a quantitative measure of symptom improvement.

Secondary endpoints include the number of adverse events observed from day 2 (V1; after the first dose of the investigational medicinal product) to week 24 (V11; end of study) in the different pramipexole treatment groups. These adverse events are categorized into nonserious, serious not related to the investigational medicinal product, and serious related to the investigational medicinal product. The collection and analysis of these data points will be conducted at specified timepoints to ensure comprehensive monitoring of both efficacy and safety throughout the trial duration.