Invesigator-initiated phase 2 study to evaluate efficacy and safety of pyridoxamine in patients with premenstrual symdromes (PMS) and premenstrual dysphoric disorder (PMDD)

JRCT ID: jRCT2021200026

Registered date:10/11/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Premenstrual Syndrome and Premenstrual Dysphoric Disorder
• Date of first enrollment: 22/09/2021
• Target sample size: 105
• Study type: Interventional

Intervention(s)

Placebo lead-in phase: RS8001 placebo capsules (3 capsules orally after breakfast and 2 capsules after dinner, twice daily)
Double-blind phase: RS8001 300 mg capsules (twice daily, 3 capsules after breakfast and 2 capsules after dinner), RS8001 240 mg capsules (twice daily, 3 capsules after breakfast and 2 capsules after dinner), or RS8001 placebo capsules (twice daily, 3 capsules after breakfast and 2 capsules after dinner)

Outcome(s)

• Primary Outcome: Luteal phase DRSP negative mood score (core symptoms of PMDD: sum of depression, anxiety, lability, and anger/irritability, change from Visit3)

Secondary Outcome

(1) CGI-S (Clinical Global Impressions-Severity; assessment of disease severity)
(2)Clinical Global Impressions-I (CGI-I; Assessment of disease symptom improvement)
(3) Luteal phase DRSP subscale score (change from Visit 3)
(4) Luteal phase DRSP total score (change from Visit 3)
(5) Hospital Anxiety and Depression Scale (HADS; Anxiety Depression Assessment)
(6) Luteal phase EQ5D (EuroQol 5 Dimension; a comprehensive measure of health-related quality of life)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 45age old
• Gender: Female

Include criteria

1. Provisional registration
(1) A patient with written informed consent
(2) A patient diagnosed with PMDD based on the DSM-5 diagnostic criteria for PMDD or diagnosed as having moderate and severe psychiatric symptoms associated with PMS based on the ACOG diagnostic criteria for PMS
(3) A patient with moderate to severe suspected PMS or suspected PMDD on the Premenstrual Symptoms Questionnaire (PSQ) assessment
(4) A patient over 20 years of age and under 45 years of age at the time of obtaining informed consent.
(5) A patient who is able to attend outpatient department throughout the study period
(6) A patient with a regular menstrual cycle between 25 and 38 days.
(7) A patient who agrees to use appropriate contraception on a regular basis from the time of informed consent throughout the study period.
(8) A patient who meets predetermined criteria as assessed by Daily Record of Severity of Problems (DRSP; ePRO or EDC between Visit 0 and Visit 2). However, if the criteria are not met solely by the degree of social disability, such patient will be additionally observed for another cycle.

2. Full registration
(9) A patient who meets predetermined criteria as assessed by Daily Record of Severity of Problems (DRSP; ePRO or EDC between Visit 2 and Visit 3)

Exclude criteria

(1) A patient who took oral contraceptives or hormone preparations containing estrogen and progesterone within 30 days prior to informed consent.
(2) A patient who was treated with antidepressants (tricyclics, tetracyclics, SSRIs, SNRIs, NaSSA) or herbal medicines within 2 weeks prior to informed consent
(3) A patient who is taking vitamin B6-containing preparations or supplements, dried chestberry extracts, aminophylline, theophylline, choline theophylline, levodopa, oxytocin-containing preparations, folic acid-containing preparations, typical antipsychotics (butyrophenones, phenothiazines, benzamides), anti-anxiety medications (Bbenzodiazepines, serotonergics), or any of the ADHD medications (methylphenidate, atomoxetine, guanfacine) , since obtaining informed consent,
(4)A patients who does not agree that the dosing regimen of atypical antipsychotics (serotonin and dopamine blockers, multimodal antipsychotics, and dopamine partial agonists), sleep medications (benzodiazepines, non-benzodiazepines, melatonin receptor agonists, and orexin receptor antagonists), and antiepileptic drugs cannot be changed during the study period.
(5) A patient who is expected to use two or more sleep medications (benzodiazepines, non-benzodiazepines, melatonin receptor agonists, or orexin receptor antagonists) during the study
(6)A patient with a diagnosis of schizophrenia, bipolar disorder, depressive disorders other than PMDD, anxiety, or obsessive-compulsive disorder
(7) A patient diagnosed with bipolar I disorder, bipolar II disorder, depression / major depressive disorder, and taking medications.
(8) A patient who had a seizure in the last 6 months up to the time of informed consent (Visit 0), if there are complications of epilepsy,
(9) A patient with malignant tumor, or treated for malignant tumor within 5 years before informed consent.
(10) A patient who is pregnant or breastfeeding, or who wishes to become pregnant during study period, at the time of informed consent.
(11) A patient who, in the opinion of the principal investigator/sub-investigators, is at high risk for self-harm, suicidal ideation or other symptoms that could result in poor treatment compliance, inability to complete the study, obstacles to study participation, or negative impact on safety assessments

Related Information

• Primary Sponsor: Takeda Takashi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)