Trial Outcomes & Findings for A Multinational Phase III Study of CS-8958 (MARVEL) (NCT NCT00803595)
NCT ID: NCT00803595
Last Updated: 2019-01-09
Results Overview
The time to illness alleviation which was defined as the time from the initiation of trial treatment to the beginning of the first 21.5-h period in which all influenza symptoms were "absent" or "mild." Patients recorded their severity of influenza symptoms (headache, myalgia/arthralgia, fatigue, chills/sweats, nasal symptom, sore throat, and cough) 4 times daily for 15 days. Patients whose influenza symptoms had not been alleviated at the time of their withdrawal from the study or at the end of the observation period were censored.
COMPLETED
PHASE3
1002 participants
15 days
2019-01-09
Participant Flow
This multicenter, double-blind,randomized, active-controlled trial was conducted from November 2008 through March 2009 at 117 institutions in Japan, Taiwan, Korea, and China (Hong Kong).
Full analysis set (FAS) was defined as the set of subjects who had a positive test result using the influenza rapid diagnostic kit, received at least 1 dose of the study drug, and had valid efficacy data. The data for the baseline characteristics is provided for this analysis set, not for all participants who entered the trial.
Participant milestones
| Measure |
CS-8958 High Dose 40 mg
CS-8958 powder to be inhaled - high-dose arm
|
CS-8958 Low Dose 20 mg
CS-8958 powder to be inhaled - low-dose arm
|
Oseltamivir 75 mg
oseltamivir phosphate oral capsules
|
|---|---|---|---|
|
Overall Study
STARTED
|
337
|
327
|
338
|
|
Overall Study
COMPLETED
|
322
|
319
|
322
|
|
Overall Study
NOT COMPLETED
|
15
|
8
|
16
|
Reasons for withdrawal
| Measure |
CS-8958 High Dose 40 mg
CS-8958 powder to be inhaled - high-dose arm
|
CS-8958 Low Dose 20 mg
CS-8958 powder to be inhaled - low-dose arm
|
Oseltamivir 75 mg
oseltamivir phosphate oral capsules
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
4
|
1
|
|
Overall Study
Protocol Violation
|
7
|
2
|
12
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
3
|
Baseline Characteristics
A Multinational Phase III Study of CS-8958 (MARVEL)
Baseline characteristics by cohort
| Measure |
CS-8958 High Dose 40 mg
n=334 Participants
CS-8958 powder to be inhaled - high-dose arm
|
CS-8958 Low Dose 20 mg
n=326 Participants
CS-8958 powder to be inhaled - low-dose arm
|
Oseltamivir 75 mg
n=336 Participants
oseltamivir phosphate oral capsules
|
Total
n=996 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
34.9 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
35.6 years
STANDARD_DEVIATION 11.7 • n=7 Participants
|
34.7 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
35.0 years
STANDARD_DEVIATION 11.5 • n=4 Participants
|
|
Sex: Female, Male
Female
|
155 Participants
n=5 Participants
|
164 Participants
n=7 Participants
|
158 Participants
n=5 Participants
|
477 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
179 Participants
n=5 Participants
|
162 Participants
n=7 Participants
|
178 Participants
n=5 Participants
|
519 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
|
334 Participants
n=5 Participants
|
326 Participants
n=7 Participants
|
336 Participants
n=5 Participants
|
996 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
Taiwan
|
62 participants
n=5 Participants
|
61 participants
n=7 Participants
|
63 participants
n=5 Participants
|
186 participants
n=4 Participants
|
|
Region of Enrollment
China
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
7 participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
263 participants
n=5 Participants
|
256 participants
n=7 Participants
|
266 participants
n=5 Participants
|
785 participants
n=4 Participants
|
|
Region of Enrollment
Korea, Republic of
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
5 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Laboratory confirmed influenza
Virus A/H1N1
|
218 Participants
n=5 Participants
|
215 Participants
n=7 Participants
|
212 Participants
n=5 Participants
|
645 Participants
n=4 Participants
|
|
Laboratory confirmed influenza
Virus A/H3N2
|
108 Participants
n=5 Participants
|
102 Participants
n=7 Participants
|
112 Participants
n=5 Participants
|
322 Participants
n=4 Participants
|
|
Laboratory confirmed influenza
Virus B
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Laboratory confirmed influenza
Negative
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 15 daysPopulation: Full analysis set (FAS) was defined as the set of subjects who had a positive test result using the influenza rapid diagnostic kit, received at least 1 dose of the study drug, and had valid efficacy data.
The time to illness alleviation which was defined as the time from the initiation of trial treatment to the beginning of the first 21.5-h period in which all influenza symptoms were "absent" or "mild." Patients recorded their severity of influenza symptoms (headache, myalgia/arthralgia, fatigue, chills/sweats, nasal symptom, sore throat, and cough) 4 times daily for 15 days. Patients whose influenza symptoms had not been alleviated at the time of their withdrawal from the study or at the end of the observation period were censored.
Outcome measures
| Measure |
CS-8958 High Dose 40 mg
n=334 Participants
CS-8958 powder to be inhaled - high-dose arm
|
CS-8958 Low Dose 20 mg
n=326 Participants
CS-8958 powder to be inhaled - low-dose arm
|
Oseltamivir 75 mg
n=336 Participants
oseltamivir phosphate oral capsules
|
|---|---|---|---|
|
Time to Alleviation of Influenza Illness
|
73.0 hours
Interval 68.4 to 80.8
|
85.8 hours
Interval 76.5 to 92.8
|
73.6 hours
Interval 68.5 to 83.3
|
SECONDARY outcome
Timeframe: 15 daysTime for return to normal axillary temperature was was defined as the time until the beginning of the first 21.5-hour period in which the axillary temperature returned to 36.9°C. Patients recorded their axillary temperature 4 times daily for 15 days. Patients whose axillary temperature had not been returned to 36.9°C at the time of their withdrawal from the study or at the end of the observation period were censored.
Outcome measures
| Measure |
CS-8958 High Dose 40 mg
n=334 Participants
CS-8958 powder to be inhaled - high-dose arm
|
CS-8958 Low Dose 20 mg
n=326 Participants
CS-8958 powder to be inhaled - low-dose arm
|
Oseltamivir 75 mg
n=336 Participants
oseltamivir phosphate oral capsules
|
|---|---|---|---|
|
Time for Body Temperature to Return to Normal
|
55.3 hours
Interval 46.6 to 64.0
|
58.0 hours
Interval 52.3 to 66.9
|
54.7 hours
Interval 48.2 to 62.2
|
Adverse Events
CS-8958 High Dose 40 mg
CS-8958 Low Dose 20 mg
Oseltamivir 75 mg
Serious adverse events
| Measure |
CS-8958 High Dose 40 mg
n=337 participants at risk
CS-8958 powder to be inhaled - high-dose arm
|
CS-8958 Low Dose 20 mg
n=326 participants at risk
CS-8958 powder to be inhaled - low-dose arm
|
Oseltamivir 75 mg
n=336 participants at risk
oseltamivir phosphate oral capsules
|
|---|---|---|---|
|
Infections and infestations
Pneumonia
|
0.00%
0/337 • 15 days
|
0.00%
0/326 • 15 days
|
0.30%
1/336 • Number of events 1 • 15 days
|
|
Nervous system disorders
Wallenberg syndrome
|
0.00%
0/337 • 15 days
|
0.00%
0/326 • 15 days
|
0.30%
1/336 • Number of events 1 • 15 days
|
Other adverse events
| Measure |
CS-8958 High Dose 40 mg
n=337 participants at risk
CS-8958 powder to be inhaled - high-dose arm
|
CS-8958 Low Dose 20 mg
n=326 participants at risk
CS-8958 powder to be inhaled - low-dose arm
|
Oseltamivir 75 mg
n=336 participants at risk
oseltamivir phosphate oral capsules
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
26/337 • 15 days
|
5.5%
18/326 • 15 days
|
7.7%
26/336 • 15 days
|
|
Gastrointestinal disorders
Nausea
|
1.2%
4/337 • 15 days
|
2.1%
7/326 • 15 days
|
1.8%
6/336 • 15 days
|
|
Gastrointestinal disorders
Vomiting
|
0.30%
1/337 • 15 days
|
0.31%
1/326 • 15 days
|
2.4%
8/336 • 15 days
|
|
Infections and infestations
Gastroenteritis
|
1.2%
4/337 • 15 days
|
0.00%
0/326 • 15 days
|
0.00%
0/336 • 15 days
|
|
Infections and infestations
Nasopharyngitis
|
3.6%
12/337 • 15 days
|
0.92%
3/326 • 15 days
|
2.4%
8/336 • 15 days
|
|
Infections and infestations
Oral herpes
|
0.59%
2/337 • 15 days
|
0.92%
3/326 • 15 days
|
1.2%
4/336 • 15 days
|
|
Investigations
Alanine aminotransferase increase
|
1.5%
5/337 • 15 days
|
1.2%
4/326 • 15 days
|
0.60%
2/336 • 15 days
|
|
Investigations
Platelet count increased
|
0.89%
3/337 • 15 days
|
1.8%
6/326 • 15 days
|
0.30%
1/336 • 15 days
|
|
Nervous system disorders
Dizziness
|
0.89%
3/337 • 15 days
|
1.8%
6/326 • 15 days
|
0.00%
0/336 • 15 days
|
|
Nervous system disorders
Headache
|
0.30%
1/337 • 15 days
|
0.92%
3/326 • 15 days
|
1.2%
4/336 • 15 days
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.59%
2/337 • 15 days
|
0.92%
3/326 • 15 days
|
1.2%
4/336 • 15 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Principle investigator shall not publish the results of the study at any time without the prior written approval of Sponsor.
- Publication restrictions are in place
Restriction type: OTHER