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A Study of S-033188 Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza (CAPSTONE 1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Shionogi Inc. ( Shionogi )
ClinicalTrials.gov Identifier:
NCT02954354
First received: October 27, 2016
Last updated: March 30, 2017
Last verified: March 2017
  Purpose
The primary objective of this study is to evaluate the efficacy of a single, oral dose of S-033188 compared with placebo by measuring the time to alleviation of symptoms in patients with uncomplicated influenza virus infection.

Condition Intervention Phase
Influenza
Drug: S-033188
Drug: Placebo to S-033188
Drug: Oseltamivir
Drug: Placebo to Oseltamivir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Otherwise Healthy Patients With Influenza

Resource links provided by NLM:


Further study details as provided by Shionogi Inc.:

Primary Outcome Measures:
  • Time to alleviation of symptoms [ Time Frame: From Day 1 pretreatment (baseline) up to Day 14 ]
    Time to alleviation of symptoms is defined as the time between the initiation of the study treatment and the alleviation of influenza symptoms. The alleviation of influenza symptoms is defined as the time when all of 7 influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) have been assessed by the patient as being alleviated at each prespecified time point.


Secondary Outcome Measures:
  • Percentage of participants positive for influenza virus titer at each time point [ Time Frame: Days 1, 2, 3, 5 and 9 ]
    Defined as the percentage of patients whose virus titer is not less than the lower limit of quantification among those assessed for virus titer.

  • Percentage of participants positive for influenza virus by RT-PCR at each time point [ Time Frame: Days 1, 2, 3, 5 and 9 ]
    Defined as the percentage of patients with detectable virus ribonucleic acid (RNA) measured by reverse transcription polymerase chain reaction (RT-PCR).

  • Change from baseline in virus titer at each time point [ Time Frame: From Day 1 pretreatment to Days 2, 3, 5, and 9 ]
    Virus titer is measured by tissue culture.

  • Change from baseline in virus RNA (RT-PCR) at each time point [ Time Frame: From Day 1 pretreatment to Days 2, 3, 5, and 9 ]
    Virus RNA is measured by reverse transcription polymerase chain reaction (RT-PCR).

  • Area under the curve (AUC) adjusted by baseline in virus titer [ Time Frame: Day 1 to Day 9 ]
    Defined as AUC of change from baseline in virus titer. The AUC is calculated using the trapezoidal method.

  • Area under the curve (AUC) adjusted by baseline of virus RNA [ Time Frame: Day 1 to Day 9 ]
    Defined as AUC of change from baseline in virus RNA. The AUC is calculated using the trapezoidal method.

  • Time to cessation of viral shedding by virus titer [ Time Frame: Day 1 to Day 9 ]
    Defined as the time between the initiation of the study treatment and first time when the virus titer is below the limit of quantification (BLQ).

  • Time to cessation of viral shedding by virus RNA [ Time Frame: Day 1 to Day 9 ]
    Defined as the time between the initiation of the study treatment and first time when the virus RNA is below the limit of quantification (BLQ) measured by RT-PCR

  • Percentage of participants whose symptoms have been alleviated at each time point [ Time Frame: Days 2, 3, 4, 5, 6, 9, and 15 ]
  • Time to alleviation of the 4 systemic symptoms [ Time Frame: Initiation of study treatment up to Day 14 ]
    Defined as the time between the initiation of the study treatment and the alleviation of the 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue).

  • Time to alleviation of the 3 respiratory symptoms [ Time Frame: Initiation of study treatment up to Day 14 ]
    Defined as the time between the initiation of the study treatment and the alleviation of the 3 respiratory symptoms (cough, sore throat and nasal congestion).

  • Change from baseline in composite symptom score at each time point [ Time Frame: Day 1 pretreatment to morning and evening on Days 2 to 9 and evening on Days 10 to 14 ]
    Defined as the change from Day 1 pretreatment (baseline) in the total score of 7 influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) as assessed by the patient.

  • Time to resolution of fever [ Time Frame: Initiation of study treatment up to Day 14 ]
    Defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever is defined as the time when the patient's self-measured axillary temperature becomes less than 37ºC.

  • Percentage of participants reporting normal temperature at each time point [ Time Frame: Days 1 to 3 at morning, noon, evening and bedtime, Days 4 to 14 morning and evening ]
    Defined as the percentage of patients whose axillary temperature drops to less than 37ºC after the initiation of the study.

  • Body temperature at each time point [ Time Frame: Days 1 to 3 at morning, noon, evening and bedtime, Days 4 to 14 morning and evening ]
  • Time to alleviation of individual symptoms [ Time Frame: Initiation of study treatment up to Day 14 ]
    Defined as the time between the initiation of the study treatment and the alleviation of individual symptoms.

  • Time to return to preinfluenza health status [ Time Frame: Initiation of study treatment up to Day 14 ]
    Patients will be asked to record their preinfluenza health status (for someone your age and your health condition). Return to preinfluenza health status is defined as time from the initiation of the study treatment to the time to return to preinfluenza health status.

  • Percentage of participants with influenza-related complications [ Time Frame: Initiation of study treatment up to Day 14 ]
    Defined as the percentage of patients in the analysis population who experience each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment.

  • Number of participants with adverse events (AEs) [ Time Frame: Day 1 to Day 22 plus or minus 3 days ]
    The incidence of AEs in patients with influenza after S-033188, after oseltamivir, and after placebo.


Estimated Enrollment: 1494
Study Start Date: November 2016
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adults: S-033188
Participants aged 20 to 64 years will receive two or four 20-mg S-033188 tablets orally on Day 1 and one oseltamivir placebo capsule orally twice a day (BID) on Days 1 to 5.
Drug: S-033188
2 to4 X 20-mg tablets taken orally
Drug: Placebo to Oseltamivir
Placebo capsules matching oseltamivir 75-mg capsules
Active Comparator: Adults: Oseltamivir
Participants aged 20 to 64 years will receive 75 mg oseltamivir twice a day on Days 1 to 5 and two or four S 033188 placebo tablets on Day 1.
Drug: Placebo to S-033188
2 to4 X 20-mg tablets taken orally
Drug: Oseltamivir
75-mg capsules taken orally
Other Name: Tamiflu®
Placebo Comparator: Adults: Placebo
Participants aged 20 to 64 years will receive two or four S 033188 placebo tablets on Day 1 and one oseltamivir placebo capsule orally twice a day on Days 1 to 5.
Drug: Placebo to S-033188
2 to4 X 20-mg tablets taken orally
Drug: Placebo to Oseltamivir
Placebo capsules matching oseltamivir 75-mg capsules
Experimental: Adolescents: S-033188
Participants aged 12 to 19 years will receive two or four S 033188 20-mg tablets on Day 1.
Drug: S-033188
2 to4 X 20-mg tablets taken orally
Placebo Comparator: Adolescents: Placebo
Participants aged 12 to 19 years will receive two or four S-033188 placebo tablets on Day 1.
Drug: Placebo to S-033188
2 to4 X 20-mg tablets taken orally

  Eligibility

Ages Eligible for Study:   12 Years to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who are able to understand the study and comply with all study procedures, and willing to provide written informed consent/assent prior to the predose examinations appropriately. As for adolescent patients, informed consent/assent of voluntary participation should be obtained in accordance with local requirements
  2. Male or female patients aged ≥ 12 to ≤ 64 years at the time of signing the informed consent/assent form.
  3. Patients with a diagnosis of influenza virus infection confirmed by all of the following:

    1. Fever ≥ 38ºC (axillary) in the predose examinations or > 4 hours after dosing of antipyretics if they were taken
    2. At least one of the following general systemic symptoms associated with influenza are present with a severity of moderate or greater

      • Headache
      • Feverishness or chills
      • Muscle or joint pain
      • Fatigue
    3. At least one of the following respiratory symptoms associated with influenza are present with a severity of moderate or greater

      • Cough
      • Sore throat
      • Nasal congestion
  4. The time interval between the onset of symptoms and the predose examinations is 48 hours or less. The onset of symptoms is defined as either:

    1. Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature)
    2. Time when the patient experiences at least one general or respiratory symptom
  5. Women of childbearing potential who agree to use a highly effective method of contraception for 3 months after the first dose of study drug

Exclusion Criteria:

  1. Patients with severe influenza virus infection requiring inpatient treatment.
  2. Patients aged ≥ 20 years with known allergy to oseltamivir (Tamiflu®).
  3. Patients with any of the following risk factors

    1. Women who are pregnant or within 2 weeks post-partum
    2. Residents of long-term care facilities (eg, welfare facilities for the elderly, nursing homes)
    3. Chronic respiratory diseases including bronchial asthma
    4. Neurological and neurodevelopmental disorders including disorders of the brain, spinal cord, peripheral nerve, and muscle (eg, cerebral palsy, epilepsy [seizure disorders], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)
    5. Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease), excluding hypertension without any other heart-related symptoms)
    6. American Indians and Alaskan natives
    7. Blood disorders (such as sickle cell disease)
    8. Endocrine disorders (including diabetes mellitus)
    9. Kidney disorders
    10. Liver disorders
    11. Metabolic disorders
    12. Compromised immune system (including patients receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus [HIV] infection)
    13. Morbid obesity (body mass index [BMI] ≥ 40)
  4. Patients unable to swallow tablets or capsules.
  5. Patients who have previously received S-033188.
  6. Patients weighing < 40 kg
  7. Patients who have been exposed to an investigational drug within 30 days prior to the predose examinations.
  8. Women who are breastfeeding or have a positive pregnancy test in the predose examinations. The following female patients who have documentation of either a or b below do not need to undergo a pregnancy test in the predose examinations:

    1. Postmenopausal (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test) women
    2. Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation
  9. Patients with concurrent infections requiring systemic antimicrobial and/or antiviral therapy at the predose examinations.
  10. Patients who have received peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, or amantadine within 30 days prior to the predose examinations.
  11. Patients who have received an investigational monoclonal antibody for a viral disease in the last year.
  12. Patients with severe underlying diseases.
  13. Patients with known creatinine clearance ≤ 60 mL/min.
  14. Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02954354

  Show 270 Study Locations
Sponsors and Collaborators
Shionogi
Investigators
Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi
  More Information

Responsible Party: Shionogi
ClinicalTrials.gov Identifier: NCT02954354     History of Changes
Other Study ID Numbers: 1601T0831
Study First Received: October 27, 2016
Last Updated: March 30, 2017

Keywords provided by Shionogi Inc.:
Flu
S-033188
Oseltamivir
Tamiflu®

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 24, 2017