A 13-week clinical trial which compares the effectiveness and safety of a not yet approved drug called DS-5565 versus placebo and versus an approved drug, in patients with pain related to fibromyalgia

• Register: EUCTR
• Last refreshed on: 9 January 2017
• Main ID: EUCTR2013-005163-10-LT
• Date of registration: 25/11/2014
• Prospective Registration: Yes
• Primary sponsor: Daiichi Sankyo Development Ltd
• Public title: A 13-week clinical trial which compares the effectiveness and safety of a not yet approved drug called DS-5565 versus placebo and versus an approved drug, in patients with pain related to fibromyalgia
• Scientific title: A Randomized, Double-Blind, Placebo- and Active-Controlled Study of DS-5565 in Subjects with Pain Associated with Fibromyalgia
• Date of first enrolment: 18/02/2015
• Target sample size: 1205
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005163-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Croatia, Estonia, Hungary, India, Latvia, Lithuania, New Zealand, Romania, Russian Federation, Slovakia, United Kingdom, United States

Contacts

• Name: Clinical Trial Application
• Affiliation: Daiichi Sankyo Development Ltd

• Name: Clinical Trial Application
• Affiliation: Daiichi Sankyo Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age = 18 years
2. Able to give written informed consent
3. Able to complete subject-reported questionnaires per the investigator’s judgment
4. At screening, subjects must meet the 1990 American College of Rheumatology (ACR) criteria for FM, i.e. widespread pain present for at least 3 months and pain in at least 11 of 18 specific tender point sites. In addition, the 2010 ACR criteria must be met:
• Widespread pain index (WPI) = 7 and symptom severity (SS) scale score = 5, or WPI 3 to 6 and SS scale score = 9
• Symptoms have been present at a similar level for at least 3 months
• The subject does not have a disorder that would otherwise explain the pain
5. ADPS of = 4 on the 11-point numeric rating scale (NRS) over the past 7 days prior to randomization (based on completion of at least 4 daily pain diaries during the 7-day baseline period prior to randomization)
6. Subject must have documented evidence of a fundoscopic examination (with pupil dilation) or a scanning laser ophthalmoscopy examination within 12 months prior to screening or at screening.
7. Women of child-bearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy during the study and for 4 weeks after study completion
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 964
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 241

Exclusion criteria:
1. Clinically significant unstable neurologic, psychiatric, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (e.g., severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) or any other concurrent disease within 12 months prior to screening that in the opinion of the investigator would interfere with study participation or assessment of safety and tolerability.
2. Anticipation of initiation or significant change to normal daily exercise routines or need for ongoing use of concomitant medications or non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety
3. Unable to undergo pre-study washout of prohibited concomitant medications
4. Subjects who are at risk of suicide as defined by their responses to the Columbia-suicide severity rating scale (C-SSRS) or in the opinion of the investigator. Note: Patients answering “yes” to any of the questions about active suicidal ideation/intent/behaviors occurring within the past 12 months must be excluded (C-SSRS Suicide Ideation section – Questions 3, 4, or 5; C-SSRS Suicidal Behavior section, any of the suicide behaviors questions). Such patients should be referred immediately to a mental health professional for appropriate evaluation.
5. Current severe or uncontrolled major depressive disorder or anxiety disorders as assessed by the Mini-international Neuropsychiatric Interview (MINI) interview (Version 6.0) at screening are excluded, but mild to moderate major depression or anxiety disorders are permitted provided that the investigator assesses the patient as clinically stable and appropriate for entry into the study.
6. Any diagnosis of lifetime bipolar disorder or psychotic disorder
7. Subjects with pain due to other conditions (e.g., diabetic peripheral neuropathic pain or post-herpetic neuralgia) that in the opinion of the investigator, would confound assessment or self-evaluation of the pain associated with FM.
8. Subjects with pain due to any widespread inflammatory musculoskeletal disorder (e.g., rheumatoid arthritis, lupus) or widespread rheumatic disease other than FM.
9. Abuse or dependence of prescription medications, street drugs, or alcohol within the last 1 year
10. Any history of a malignancy other than basal cell carcinoma within the past 5 years
11. A diagnosis of untreated sleep apnea or initiation of treatment for sleep apnea within the past 3 months
12. Known hypersensitivity to alpha2-delta (a2d) ligands or other components of the study medications. Note: Prior exposure to DS-5565 is allowed, as long as hypersensitivity to DS-5565 was not observed.
13. Pregnancy or breast-feeding, or intent to become pregnant during the study period
14. Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents.
15. Subject is an employee of the study center, an immediate family member* of an employee of the study center or an employee of Daiichi Sankyo, INC Research or any of the study vendors supporting this study. *(spouse, parent, child, or sibling, whether biological or legally adopted)
16. Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the investigator to be unlikely to complete the study.
17. Abnormal investigative tests (i.e.

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

DS-5565 is being developed for the treatment of pain associated with fibromyalgia (FM).
MedDRA version: 19.0 Level: PT Classification code 10048439 Term: Fibromyalgia System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

Intervention(s)

Product Name: DS-5565
Product Code: DS-5565
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Mirogabalin
Current Sponsor code: DS-5565
Other descriptive name: DS-5565
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Lyrica
Pharmaceutical Form: Capsule
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Other descriptive name: PREGABALIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Lyrica
Pharmaceutical Form: Capsule
INN or Proposed INN: Pregabalin
CAS Number: 148553-50-8
Other descriptive name: PREGABALIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To compare change in weekly average daily pain score (ADPS) from baseline to Week 13 in subjects receiving either dose of DS-5565 versus placebo.
Weekly ADPS is based on daily pain scores reported by the subject that best describes his or her worst pain over the previous 24 hours.

Primary end point(s): Change in weekly ADPS from baseline to Week 13 (Visit 11) for either dose of DS-5565 versus placebo

Timepoint(s) of evaluation of this end point: Weekly ADPS is based on daily pain scores reported by the subject (from baseline to Week 13) that best describes his or her worst pain over the previous 24 hours.
The final evaluation of the primary endpoint will be done at Week 13.

Secondary Objective: The key secondary objectives are:
• To compare change in ADPS from baseline to Week 13 in subjects receiving either dose of DS-5565 versus pregabalin
• To compare the proportion of subjects with = 30% reduction from baseline to Week 13 in ADPS receiving either dose of DS-5565 versus placebo
• To compare the proportion of subjects with = 50% reduction from baseline to Week 13 in ADPS receiving either dose of DS-5565 versus placebo
• To assess the effects of either dose of DS-5565 versus placebo on patient global impression of change (PGIC) at Week 13
• To evaluate the change in fibromyalgia impact questionnaire (FIQ) total score from baseline to Week 13 in subjects receiving either dose of DS-5565 versus placebo

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The final evaluation of all the secondary endpoints mentioned above will be done at Week 13.

Secondary end point(s): The key secondary endpoints are:
• Change in ADPS from baseline to Week 13 (Visit 11) in subjects receiving either dose of DS-5565 versus pregabalin
• Proportion of subjects with = 30% reduction from baseline to Week 13 (Visit 11) in ADPS receiving either dose of DS-5565 versus placebo
• Proportion of subjects with = 50% reduction from baseline to Week 13 (Visit 11) in ADPS receiving either dose of DS-5565 versus placebo
• Effects of either dose of DS-5565 versus placebo on PGIC at Week 13 (Visit 11)
• Change in FIQ total score from baseline to Week 13 (Visit 11) in subjects receiving either dose of DS-5565 versus placebo

The remaining secondary endpoints are:
• Changes in multidimensional fatigue inventory (MFI-20) parameters from baseline to Week 13 (Visit 11) for DS-5565 versus placebo
• Changes from baseline to Week 13 (Visit 11) in hospital anxiety and depression scale (HADS) depression and anxiety scores for DS-5565 versus placebo
• Changes in short form 36 (SF-36) parameters from baseline to Week 13 (Visit 11) for DS-5565 versus placebo
• Changes in EuroQoL instrument 5 domains (EQ-5D) parameters from baseline to Week 13 (Visit 11) for DS-5565 versus placebo
• Changes in medical outcomes study (MOS) and average daily sleep interference score (ADSIS) from baseline to Week 13 (Visit 11) for DS-5565 versus placebo
• Changes in brief pain inventory short form (BPI-SF9) parameters from baseline to Week 13 (Visit 11) for DS-5565 versus placebo
• Proportion of days rescue medication was used (number of days rescue medication used divided by total number of study days)

Secondary ID(s)

2013-005163-10-GB

DS5565-A-E311

Source(s) of Monetary Support

Daiichi Sankyo Development Ltd