E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
DS-5565 is being investigated for the treatment of pain associated with fibromyalgia (FM) in subjects with chronic kidney disease. |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of pain related to fibromyalgia in patients with kidney disease. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048439 |
E.1.2 | Term | Fibromyalgia |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the safety and tolerability of subjects with FM and moderate to severe renal dysfunction during 13 weeks of renally adjusted dosing of DS-5565 compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
• To compare change in weekly average pain as assessed by average daily pain score (ADPS) from baseline measured at randomization 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 the worst pain over the previous 24 hours
•To assess the effects of DS-5565 on patient global impression of change (PGIC) at Week 13/ET. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years
2. Able to give written informed consent
3. Able to complete patient-reported questionnaires per the Investigator's judgment
4. Estimated CrCl between 15-59 mL/min from serum creatinine by the central laboratory using the Cockcroft-Gault equation
5. Fibromyalgia meeting American College of Rheumatology criteria for FM:
a. Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5, or WPI 3 to 6 and SS scale score ≥ 9,
b. Pain in at least 11 of 18 specific tender point sites,
c. Symptoms have been present at a similar level for at least 3 months, and
d. The subject does not have a disorder that would otherwise explain the pain
6. ADPS of ≥ 4 on the 11-point numeric rating scale (NRS) over the 7 days prior to randomization (based on completion of at least 4 daily pain assessments during the 7-day baseline period prior to randomization)
7. Women of child bearing potential (WOCBP) must be using adequate methods of contraception (as detailed in Section 4.1.3) to avoid pregnancy during the study and for 4 weeks after study completion. |
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E.4 | Principal exclusion criteria |
1. Need for ongoing use of concomitant chronic pain medications or any new non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety, including neurolytic treatments (destruction of nerves by chemicals, heat, cold) or surgery, intrathecal pumps, spinal cord stimulators or psychological support
within the previous year. Also excluded: topical capsaicin within 6 months; or systemic corticosteroids within 3 months of baseline period.
2. Unable to undergo pre-study washout of prohibited concomitant medications
3. Subjects with recent history (i.e., within 1 year prior to screening) of alcohol abuse or illicit drug use (cocaine, heroin, marijuana [including medical, prescribed], etc.)
4. Use of any selective serotonin reuptake inhibitor (SSRI), unless the subject has been on a stable dose
for ≥ 90 days prior to screening and is not anticipated to need any dose adjustment during the course of the study
5. Subjects with severe or uncontrolled depression that, in the judgment of the Investigator, makes the subject inappropriate for entry into the study
6. Significant neurological or psychiatric disorder unrelated to neuropathic pain
7. Other severe pain (eg, sciatica, rheumatoid arthritis) that might impair the assessment of neuropathic
pain
8. CrCl ≥ 60 mL/min estimated from serum creatinine by the central laboratory using the Cockcroft-Gault
equation.
9. Subjects who are on hemodialysis or who require hemodialysis before the follow-up assessment;
acute renal failure; history of kidney transplant
10. Any history of a malignancy other than basal cell carcinoma within the past 5 years
11. Clinically significant unstable neurologic, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (eg, severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) within 12 months prior to screening
12. Pregnancy or breast feeding or intent to become pregnant during the study period
13. Known hypersensitivity to α2δ 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.
14. Clinically significant ECG abnormalities at the Screening Visit
15. Subjects who are at risk of suicide, as defined by their responses to the C-SSRS or in the opinion of the Investigator. Note: Subjects answering "yes" to any of the questions about active suicidal ideation/intent/behaviors that occurred 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 subjects should be referred immediately to a mental health professional for appropriate evaluation.
16. Subjects who are unlikely to comply with the protocol (eg, uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study)
17. Subject is currently enrolled in, or it has been fewer than 30 days since ending, another investigational device or drug study or is receiving another investigational agent.
18. Subjects who are employees or immediate family of employees of the study site, Sponsor, or contract research organization (CRO)
19. Screening laboratory values outside the limits listed in the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary safety objective is the safety and tolerability of renally adjusted doses of DS-5565 versus placebo.
Specific safety endpoints assessed include:
• All treatment-emergent adverse events (TEAEs)
• Change in clinical laboratory evaluations from baseline measured at randomization to Week 13/ET for DS-5565 versus placebo
• Change in neurological examinations from baseline to Week 13/ET for DS-5565 versus placebo
• Change in electrocardiograms from baseline to Week 13/ET for DS-5565 versus placebo
• Change in Columbia-Suicide Severity Rating Scale (C-SSRS) from baseline to Week 13/ET for DS-5565 versus placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final evaluation of the primary endpoint will be done at Week 13/ET. |
|
E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include:
• Changes in ADPS from baseline measured at randomization to Week 13/ET for DS-5565 versus placebo. Weekly ADPS is based on daily pain scores reported by the subject that best describes the worst pain over the previous
24 hours.
• Proportion of subjects with improvement in overall status at Week 13/ET as assessed by PGIC for DS-5565 versus placebo. |
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E.5.2.1 | 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 secondary endpoints will be done at Week 13/ET. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Czech Republic |
France |
Germany |
Hungary |
Poland |
Romania |
Slovakia |
South Africa |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |