DS-5565 Phase III Study for Renal Impairment in Japanese Subjects

• Sponsor: Daiichi Sankyo Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02607280
• Collaborator: CMIC Co, Ltd. Japan (Industry)
• Enrollment: 35
• Location: 1
• Arm: 1
• Actual Duration (Months): 15
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

Investigate the safety and efficacy of DS-5565 in Japanese subjects with Diabetic Peripheral Neuropathic Pain (DPNP) with renal impairment or Post-Herpetic Neuralgia (PHN) with renal impairment.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Peripheral Neuropathic Pain; Post-herpetic Neuralgia	Drug: DS-5565	Phase 3

Detailed Description

The primary objective is the safety and tolerability of DS-5565 in Japanese subjects with moderate to severe renal impairment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A JAPANESE, PHASE 3, OPEN-LABEL, 14-WEEK STUDY OF DS-5565 IN PATIENTS WITH PAIN ASSOCIATED WITH DIABETIC PERIPHERAL NEUROPATHY WITH RENAL IMPAIRMENT OR POST-HERPETIC NEURALGIA WITH RENAL IMPAIRMENT
• Actual Study Start Date: Dec 1, 2015
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DS-5565 group DS-5565 15 mg (for moderate renal impairment) or 7.5 mg (for severe renal impairment), oral administration, Treatment period; 2-weeks titration and 12-weeks fixed dose	Drug: DS-5565; DS-5565 15 mg (for moderate renal impairment) or 7.5 mg (for severe renal impairment), oral administration, Treatment period; 2-weeks titration and 12-weeks fixed dose; Other Names: mirogabalin

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Average Daily Pain Score (ADPS) at Each Week [Baseline to Week 14]

   Each participant recorded a pain score in the electronic patient diary once daily from the day after the screening visit (Visit 1) to the end of treatment/early termination visit (Visit 10). Prior to taking the study drug each morning, the participant selected the number that best described his or her pain over the past 24 hours on a scale of 0 (no pain) to 10 (worst possible pain). Higher ADPS scores indicated worse outcome. ADPS was the weekly average pain score based on the pain scores from the electronic patient diaries (Pain diary). In this outcome, the change from baseline in ADPS is being reported with negative values representing improvements in average daily pain. The larger the negative value (ie. improvement), the greater the improvement in average daily pain.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At screening, creatinine clearance (using the Cockcroft-Gault equation): 15-59 mL/min

• At screening, a pain scale of ≥ 40 mm

• Type 1 or type 2 diabetes mellitus at screening (for patients with diabetic peripheral neuropathic pain DPNP only)-. Painful distal symmetric polyneuropathy (for patients with DPNP only)

• post-herpetic neuralgia PHN defined as pain present for more than 3 months after herpes zoster skin rash at screening (for patients with PHN only)

Exclusion Criteria:

• HbA1c (National Glycohemoglobin Standardization Program) > 10.0% (for patients with DPNP only)

• Previous use of neurolytic block (for patients with PHN only)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shonan Kamakura General Hospital	Kamakura-shi	Kanagawa	Japan	247-8533

Sponsors and Collaborators

• Daiichi Sankyo Co., Ltd.
• CMIC Co, Ltd. Japan

Investigators

• Study Director: Clinical Study Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 1, 2016

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02607280
• Other Study ID Numbers: DS5565-A-J313
• First Posted: Nov 18, 2015
• Last Update Posted: May 13, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo Co., Ltd.: Diabetic peripheral neuropathic pain; post-herpetic neuralgia; renal impairment
• Additional relevant MeSH terms: Neuralgia; Neuralgia, Postherpetic; Diabetic Neuropathies; Renal Insufficiency

Study Results

Participant Flow

Recruitment Details	A total of 35 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study from December 2015 to March 2017 at 1 clinic site in Japan.

Arm/Group Title	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	Participants with moderate RI (creatinine clearance: 30 to 59 mL/min) received DS-5565 2.5 mg BID for the first week and DS-5565 5 mg BID for the second week of the titration period and subsequently received a fixed dose of DS-5565 7.5mg BID for 12 weeks.	Participants with severe RI (creatinine clearance: 15 to 29 mL/min) received DS-5565 2.5 mg QD for the first week and DS-5565 5 mg QD for the second week of the titration period and subsequently received the fixed dose of DS-5565 7.5 mg QD for 12 weeks.
Period Title: Overall Study
STARTED	30	5
Received Study Drug	30	5
COMPLETED	26	4
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Moderate Renal Impairment	Severe Renal Impairment	Total
Arm/Group Description	Participants with moderate RI (creatinine clearance: 30 to 59 mL/min) received DS-5565 2.5 mg BID for the first week and DS-5565 5 mg BID for the second week of the titration period and subsequently received a fixed dose of DS-5565 7.5mg BID for 12 weeks.	Participants with severe RI (creatinine clearance: 15 to 29 mL/min) received DS-5565 2.5 mg QD for the first week and DS-5565 5 mg QD for the second week of the titration period and subsequently received the fixed dose of DS-5565 7.5 mg QD for 12 weeks.	Total of all reporting groups
Overall Participants	30	5	35
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 10%	0 0%	3 8.6%
>=65 years	27 90%	5 100%	32 91.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.8 (7.69)	71.0 (4.06)	73.4 (7.31)
Sex: Female, Male (Count of Participants)
Female	6 20%	1 20%	7 20%
Male	24 80%	4 80%	28 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	30 100%	5 100%	35 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	30 100%	5 100%	35 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Japan	30 100%	5 100%	35 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Average Daily Pain Score (ADPS) at Each Week
Description	Each participant recorded a pain score in the electronic patient diary once daily from the day after the screening visit (Visit 1) to the end of treatment/early termination visit (Visit 10). Prior to taking the study drug each morning, the participant selected the number that best described his or her pain over the past 24 hours on a scale of 0 (no pain) to 10 (worst possible pain). Higher ADPS scores indicated worse outcome. ADPS was the weekly average pain score based on the pain scores from the electronic patient diaries (Pain diary). In this outcome, the change from baseline in ADPS is being reported with negative values representing improvements in average daily pain. The larger the negative value (ie. improvement), the greater the improvement in average daily pain.
Time Frame	Baseline to Week 14

Outcome Measure Data

Analysis Population Description

ADPS was assessed in the All Enrolled Participants.

Arm/Group Title	Moderate Renal Impairment	Severe Renal Impairment
Arm/Group Description	Participants with moderate RI (creatinine clearance: 30 to 59 mL/min) received DS-5565 2.5 mg BID for the first week and DS-5565 5 mg BID for the second week of the titration period and subsequently received a fixed dose of DS-5565 7.5mg BID for 12 weeks.	Participants with severe RI (creatinine clearance: 15 to 29 mL/min) received DS-5565 2.5 mg QD for the first week and DS-5565 5 mg QD for the second week of the titration period and subsequently received the fixed dose of DS-5565 7.5 mg QD for 12 weeks.
Measure Participants	30	5
Week 1	-0.14 (0.680)	-0.20 (0.217)
Week 2	-0.37 (0.940)	-0.50 (0.937)
Week 3	-0.85 (1.294)	-1.83 (1.859)
Week 4	-1.13 (1.318)	-2.07 (2.375)
Week 5	-0.90 (1.361)	-1.89 (2.278)
Week 6	-0.92 (1.285)	-1.82 (1.922)
Week 7	-1.22 (1.402)	-1.93 (1.732)
Week 8	-1.29 (1.554)	-2.04 (1.735)
Week 9	-1.36 (1.540)	-2.21 (1.980)
Week 10	-1.33 (1.562)	-2.32 (1.914)
Week 11	-1.43 (1.664)	-2.07 (1.584)
Week 12	-1.59 (1.636)	-2.10 (1.728)
Week 13	-1.84 (1.650)	-2.25 (1.700)
Week 14	-1.90 (1.697)	-2.52 (2.026)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Moderate Renal Impairment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean change from baseline at Week 14
	Estimated Value	-1.79
	Confidence Interval	(2-Sided) 95%; -2.45 to -1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Severe Renal Impairment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean change from baseline at Week 14
	Estimated Value	-2.07
	Confidence Interval	(2-Sided) 95%; -3.77 to -0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected from baseline up to 7 days after last dose, up to 1 year 3 months.
Adverse Event Reporting Description	Any adverse event (AE) that emerges on or after first dosing and during the duration of the study treatment (having been absent prior to treatment) or worsens relative to the pre-treatment state.
Arm/Group Title	Moderate Renal Impairment		Severe Renal Impairment
Arm/Group Description	Participants with moderate RI (creatinine clearance: 30 to 59 mL/min) received DS-5565 2.5 mg BID for the first week and DS-5565 5 mg BID for the second week of the titration period and subsequently received a fixed dose of DS-5565 7.5mg BID for 12 weeks.		Participants with severe RI (creatinine clearance: 15 to 29 mL/min) received DS-5565 2.5 mg QD for the first week and DS-5565 5 mg QD for the second week of the titration period and subsequently received the fixed dose of DS-5565 7.5 mg QD for 12 weeks.
All Cause Mortality
	Moderate Renal Impairment		Severe Renal Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/5 (0%)
Serious Adverse Events
	Moderate Renal Impairment		Severe Renal Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/5 (0%)
Cardiac disorders
Angina pectoris	1/30 (3.3%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Moderate Renal Impairment		Severe Renal Impairment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/30 (56.7%)		3/5 (60%)
Gastrointestinal disorders
Diarrhoea	2/30 (6.7%)		0/5 (0%)
Nausea	2/30 (6.7%)		0/5 (0%)
General disorders
Oedema peripheral	2/30 (6.7%)		1/5 (20%)
Infections and infestations
Nasopharyngitis	6/30 (20%)		2/5 (40%)
Musculoskeletal and connective tissue disorders
Back pain	2/30 (6.7%)		0/5 (0%)
Nervous system disorders
Somnolence	4/30 (13.3%)		0/5 (0%)
Dizziness	2/30 (6.7%)		0/5 (0%)
Sensory disturbance	2/30 (6.7%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.