Trial Outcomes & Findings for Phase III Study of ASP2151 in Herpes Zoster Patients (NCT NCT01959841)
NCT ID: NCT01959841
Last Updated: 2018-11-27
Results Overview
The investigator assessed the Number of rashes (erythemas/papulae and vesicles/pustules). The "new lesion formation" was defined as the state in which the number of rashes is increasing.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
751 participants
Primary outcome timeframe
4days
Results posted on
2018-11-27
Participant Flow
The study was conducted at 106 sites in Japan from September 2013 to Jully 2015
Participant milestones
| Measure |
ASP2151(200 mg)
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Overall Study
STARTED
|
252
|
250
|
249
|
|
Overall Study
Full Analysis Set Included
|
247
|
243
|
245
|
|
Overall Study
Full Analysis Set Excluded
|
5
|
7
|
4
|
|
Overall Study
Reason FAS Excluding 1
|
5
|
5
|
4
|
|
Overall Study
Reason FAS Excluding 2
|
0
|
1
|
0
|
|
Overall Study
Reason FAS Excluding 3
|
0
|
1
|
0
|
|
Overall Study
COMPLETED
|
209
|
193
|
206
|
|
Overall Study
NOT COMPLETED
|
43
|
57
|
43
|
Reasons for withdrawal
| Measure |
ASP2151(200 mg)
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
3
|
2
|
|
Overall Study
Lack of Efficacy
|
5
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
2
|
3
|
|
Overall Study
Protocol Violation
|
16
|
23
|
16
|
|
Overall Study
Withdrawal by Subject
|
7
|
7
|
5
|
|
Overall Study
Clinical laboratory value
|
2
|
6
|
6
|
|
Overall Study
Platelet count below on day1 or 4
|
11
|
15
|
11
|
Baseline Characteristics
Phase III Study of ASP2151 in Herpes Zoster Patients
Baseline characteristics by cohort
| Measure |
ASP2151(200 mg)
n=247 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=243 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=245 Participants
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
Total
n=735 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
178 Participants
n=5 Participants
|
174 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
530 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
69 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
205 Participants
n=4 Participants
|
|
Age, Continuous
|
52.0 years
STANDARD_DEVIATION 16.3 • n=5 Participants
|
53.0 years
STANDARD_DEVIATION 16.2 • n=7 Participants
|
52.2 years
STANDARD_DEVIATION 15.8 • n=5 Participants
|
52.39 years
STANDARD_DEVIATION 16.09 • n=4 Participants
|
|
Sex: Female, Male
Female
|
134 Participants
n=5 Participants
|
144 Participants
n=7 Participants
|
146 Participants
n=5 Participants
|
424 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
113 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
311 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
247 Participants
n=5 Participants
|
243 Participants
n=7 Participants
|
245 Participants
n=5 Participants
|
735 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
247 Participants
n=5 Participants
|
243 Participants
n=7 Participants
|
245 Participants
n=5 Participants
|
735 Participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
247 Participants
n=5 Participants
|
243 Participants
n=7 Participants
|
245 Participants
n=5 Participants
|
735 Participants
n=4 Participants
|
|
Time from onset of rash to the first dose
within 24 hours
|
53 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
154 Participants
n=4 Participants
|
|
Time from onset of rash to the first dose
over 24 hours, within 48 hours
|
92 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
281 Participants
n=4 Participants
|
|
Time from onset of rash to the first dose
over 48 hours, within 72 hours
|
102 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
300 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 4daysPopulation: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
The investigator assessed the Number of rashes (erythemas/papulae and vesicles/pustules). The "new lesion formation" was defined as the state in which the number of rashes is increasing.
Outcome measures
| Measure |
ASP2151(200 mg)
n=247 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=243 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=245 Participants
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
The Percentage of Participants Achieving Cessation of New Lesion Formation by Day 4 of Study Treatment
|
69.6 percentage of Participants
|
81.1 percentage of Participants
|
75.1 percentage of Participants
|
SECONDARY outcome
Timeframe: 29daysPopulation: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
The investigator assessed the Number of rashes (erythemas/papulae and vesicles/pustules). The "new lesion formation" was defined as the state in which the number of rashes is increasing.
Outcome measures
| Measure |
ASP2151(200 mg)
n=247 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=243 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=245 Participants
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Time to Cessation of New Lesion Formation
|
4 days
Interval 3.0 to 5.0
|
4 days
Interval 3.0 to 4.0
|
4 days
Interval 3.0 to 4.0
|
SECONDARY outcome
Timeframe: 29daysPopulation: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
We defined the following state as "Complete crusting". 1. A condition where all lesions of erythemas/papulae, vesicles/pustules, and erosions/ulcers have disappeared, and all rashes are crusted (epithelialization of the base of crusts is not required). 2. In subjects with no formation of vesicles or pustules, a condition where all lesions of erythemas/papulae have disappeared.
Outcome measures
| Measure |
ASP2151(200 mg)
n=247 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=243 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=245 Participants
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Time to Complete Crusting
|
8 days
Interval 6.0 to 11.0
|
9 days
Interval 7.0 to 11.0
|
8 days
Interval 7.0 to 11.0
|
SECONDARY outcome
Timeframe: 29daysPopulation: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
We defined the following state as "Healing". 1. A condition where all lesions of erythemas/papulae, vesicles/pustules, and erosions/ulcers have disappeared, and complete disappearance of crusts or complete epithelialization of the base of crusts are considered to have been achieved. 2. In subjects with no formation of vesicles or pustules, a condition where all lesions of erythemas/papulae have disappeared
Outcome measures
| Measure |
ASP2151(200 mg)
n=247 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=243 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=245 Participants
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Time to Healing
|
11 days
Interval 8.0 to 15.0
|
11 days
Interval 8.0 to 15.0
|
11 days
Interval 8.0 to 16.0
|
SECONDARY outcome
Timeframe: 29daysPopulation: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
Investigators assessed the pain using NRS. The date of pain resolution is defined as the first day when all NRS scores are rated as 2 or less, and such scores are continuously observed until Day 92 or discontinuation visit.
Outcome measures
| Measure |
ASP2151(200 mg)
n=247 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=243 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=245 Participants
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Time to Pain Resolution
|
9 days
Interval 5.0 to 19.0
|
10 days
Interval 5.0 to 19.0
|
10 days
Interval 5.0 to 19.0
|
SECONDARY outcome
Timeframe: 29daysPopulation: The full analysis set(FAS).The FAS was defined as patients who were diagnosed with herpes zoster at the time of case registration, who subsequently received the study drugs, and had any efficacy variable measured.
Virus desiappearance was defined as the participants who who reached virus-negative status according to the virus isolation and culture assay or whose samples were not available because of complete crusting or healing
Outcome measures
| Measure |
ASP2151(200 mg)
n=247 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=243 Participants
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=245 Participants
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Time to Virus Disappearance
|
4 days
Interval 4.0 to 8.0
|
5 days
Interval 4.0 to 10.0
|
4 days
Interval 3.0 to 9.0
|
Adverse Events
ASP2151(200 mg)
Serious events: 1 serious events
Other events: 62 other events
Deaths: 0 deaths
ASP2151(400mg)
Serious events: 1 serious events
Other events: 64 other events
Deaths: 0 deaths
Valaciclovir
Serious events: 3 serious events
Other events: 65 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ASP2151(200 mg)
n=252 participants at risk
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=249 participants at risk
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=249 participants at risk
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Cardiac disorders
Angina pectoris
|
0.40%
1/252 • Number of events 1 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Infections and infestations
Infectious mononucleosis
|
0.00%
0/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.40%
1/249 • Number of events 1 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.40%
1/249 • Number of events 1 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Nervous system disorders
Embolic cerebral infarction
|
0.00%
0/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.40%
1/249 • Number of events 1 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.00%
0/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.40%
1/249 • Number of events 1 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.40%
1/249 • Number of events 1 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
Other adverse events
| Measure |
ASP2151(200 mg)
n=252 participants at risk
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
ASP2151(400mg)
n=249 participants at risk
once daily
ASP2151: 200 mg once daily or 400 mg once daily
|
Valaciclovir
n=249 participants at risk
1000 mg three times daily
valaciclovir: 1000 mg three times daily
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.40%
1/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.80%
2/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.0%
5/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Gastrointestinal disorders
Stomatitis
|
0.40%
1/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.8%
7/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Infections and infestations
Folliculitis
|
2.0%
5/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.00%
0/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.0%
5/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Infections and infestations
Nasopharyngitis
|
7.5%
19/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
8.8%
22/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
6.8%
17/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Investigations
Beta-N-acetyl-D-glucosaminidase increased
|
2.8%
7/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
4.4%
11/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
3.2%
8/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Investigations
Fibrin degradation products increased
|
2.8%
7/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
3.6%
9/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
4.0%
10/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Investigations
Glucose urine present
|
1.2%
3/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
1.2%
3/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.0%
5/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Investigations
Protein urine present
|
0.79%
2/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.0%
5/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.0%
5/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Investigations
Alpha 1 microglobulin increased
|
4.4%
11/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
3.6%
9/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
4.0%
10/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Nervous system disorders
Headache
|
3.6%
9/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
0.80%
2/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.8%
7/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
1.6%
4/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.0%
5/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.0%
5/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
|
Skin and subcutaneous tissue disorders
Eczema
|
2.8%
7/252 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
1.2%
3/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
2.4%
6/249 • 92 days
Participant who has not received any study drug after randomization excluded from the Number participants at Risk
|
Additional Information
linical Development Dept.
Maruho Co.,Ltd. Kyoto R&D Center
Phone: +81-75-325-3255
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place