TUC3PII-01_TU2670 Phase IIa Clinical Study

Study Overview
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Brief Summary
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This Protocol for TU2670 is to investigate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of TU2670 in subjects with moderate to severe endometriosis-associated pain.

Detailed Description
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Treatment Groups and Duration: Following a washout period of up to 12 weeks, subjects will enter a screening period of up to 12 weeks including an observation period consisting of a complete menstrual cycle. Subjects will be randomly assigned in a 1:1:1:1 ratio to receive either 12 weeks of TU2670 320 mg QD, TU2670 240 mg QD, TU2670 120 mg QD, or matching placebo. TU2670 or a matching placebo will be administered in the clinic on Day 1. Subjects in the PK subset population will also receive the following additional doses in the clinic: Day 2 (after collection of the 24-hour PK sample); the dose on the day scheduled for subsequent serial PK sample collection (Week 4 or Week 5); and the next scheduled dose (after collection of the 24-hour PK sample). All other doses can be taken by the subject at home. Following the end of treatment, subjects will be followed up for safety for 12 weeks. Statistical Methods: All formal statistical tests will be done at the 5% 2-sided significance level. Point estimates will have 2 sided 95% confidence intervals (CIs) where applicable. Where appropriate, variables will be summarized descriptively (frequency and percent will be summarized for categorical variables; n (number of available subjects), mean, standard deviation [SD], median, minimum, and maximum will be presented for continuous variables) by study visit and by treatment group. Statistical summaries will be presented for the changes from baseline to each time point in efficacy endpoints that it is applicable.

Official Title
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A Phase IIa, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of Orally Administered TU2670 in Subjects With Mod to Severe Endometriosis-Associated Pain

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: Placebo Comparator: Placebo
* Drug: Active Comparator: TU2670 320mg
* Drug: Active Comparator: TU2670 240mg
* Drug: Active Comparator: TU2670 120mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Independent Ethics Committee (IEC)-approved written informed consent/assent and privacy language as per national regulations must be voluntarily obtained from the subject. Premenopausal female subject, 18 to 45 years, inclusive Subject has moderate to severe endometriosis-related pain Exclusion Criteria: Subject has used hormonal contraceptives or other drugs with effects on gynecological endocrinology within 12 weeks Subject has been nonresponsive to GnRH-agonist or antagonist therapy for the management of endometriosis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>4 Placebo capsules | Drug: Placebo Comparator: Placebo<br>* 4 x placebo capsules, QD<br>|
| Active Comparator: TU2670 High Dose<br>320mg, QD | Drug: Active Comparator: TU2670 320mg<br>* 320mg (80mg x 4), QD<br>|
| Active Comparator: TU2670 Medium Dose<br>240 mg, QD | Drug: Active Comparator: TU2670 240mg<br>* 240mg (80mg x 3 + placebo x 1), QD<br>|
| Active Comparator: TU2670 Low Dose<br>120 mg, QD | Drug: Active Comparator: TU2670 120mg<br>* 120mg (80mg x 1 + 20mg x 2 + placebo x 1), QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall pelvic pain | Change from baseline to 12 weeks of treatment of the mean dysmenorrhea score (defined as mean overall pelvic pain score on menstrual bleeding days) as measured by the Numeric Rating Scale(minimum 0, maximum 10, higher score mean a worse outcome) over the past month. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean Numeric Rating Scale pain score | Change from baseline to 12 weeks of treatment of the mean Numeric Rating Scale pain score(minimum 0, maximum 10, higher score mean a worse outcome) for non-menstrual pelvic pain (mean Numeric Rating Scale pain score on non menstrual bleeding days) | 12 weeks | 
| mean overall pelvic pain Numeric Rating Scale pain score | Change from baseline to 12 weeks of treatment of the mean overall pelvic pain Numeric Rating Scale pain score (mean Numeric Rating Scale pain score(minimum 0, maximum 10, higher score mean a worse outcome) over all 28 days) | 12 weeks | 
| mean Numeric Rating Scale dyspareunia score | Change from baseline to 12 weeks of treatment of the mean Numeric Rating Scale((minimum 0, maximum 10, higher score mean a worse outcome) dyspareunia score | 12 weeks | 
| rescue medication | Change from baseline to 12 weeks of treatment of the use of protocol-defined rescue medication (ie, ibuprofen) | 12 weeks | 
| Time to increase of dose of rescue medication | Time to increase of dose of rescue medication from 0 week to 12 weeks | 12 weeks | 
| Time to decrease of dose of rescue medication | Time to decrease of dose of rescue medication from 0 week to 12 weeks | 12 weeks | 
| Modified Biberoglu and Behrman sign and symptom scores | Change from baseline to 12 weeks of treatment of the Modified Biberoglu and Behrman (mB&B) sign and symptom scores(minimum 0, maximum 3, higher score mean a worse outcome) | 12 weeks | 
| Patient Global Impression of Change | Patient Global Impression of Change (minimum 1, maximum 7, higher score mean a worse outcome) at 12 weeks of treatment | 12 weeks | 
| Endometriosis Health Profile-5 | Change from baseline to 12 weeks of treatment in the Endometriosis Health Profile-5 score(minimum 1(Never), maximum 5(Always), higher score mean a worse outcome) | 12 weeks | 
| 36-Item Short Form Health Survey | Change from baseline to 12 weeks of treatment of the 36-Item Short Form Health Survey(Scoring meaning is different from the questions but usually lower score mean a worse outcome) | 12 weeks | 
| Work Productivity and Activity Impairment Questionnaire: General Health | Change from baseline to 12 weeks of treatment of the Work Productivity and Activity Impairment Questionnaire: General Health (Scoring meaning is different from the questions) | 12 weeks |