A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Investigate the Efficacy and Safety of Inhaled Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Adults with Symptomatic Influenza A or B Infection

• Register: EUCTR
• Last refreshed on: 19 May 2014
• Main ID: EUCTR2013-000582-36-EE
• Date of registration: 19/08/2013
• Prospective Registration: Yes
• Primary sponsor: Biota Scientific Management Pty Ltd.
• Public title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Investigate the Efficacy and Safety of Inhaled Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Adults with Symptomatic Influenza A or B Infection
• Scientific title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Investigate the Efficacy and Safety of Inhaled Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Adults with Symptomatic Influenza A or B Infection
• Date of first enrolment: 22/08/2013
• Target sample size: 900
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000582-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Australia, Belgium, Bulgaria, Canada, Colombia, Estonia, France, Germany, Hungary, Latvia, Mexico, New Zealand, Peru, South Africa, United Kingdom, United States

Contacts

• Name: Clinical Operations
• Affiliation: Biota Scientific Management Pty Ltd.

• Name: Clinical Operations
• Affiliation: Biota Scientific Management Pty Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide written informed consent
2. Males or females aged 18–64 years, inclusive
3.A female subject is eligible to enter the study if she meets following criteria:
- not pregnant or breast feeding / lactating
- females of non-childbearing potential
- females of child bearing potential must have a negative urine pregnancy test at screening
- females of childbearing potential must agree to use adequate and highly effective methods of contraception throughout the study (See Section 4.5)
4. Male subjects with female partners of childbearing potential must use adequate and highly effective methods of contraception such as double-barrier method, from screening until 1 month after their last dose of study drug. (See Section 4.5)
5. Symptomatic presumptive influenza A or B infection defined as the presence of:
a. a fever of =38.0ºC (=100.4 ºF) at the screening visit
AND
b. =1 moderate systemic symptom (headache, feeling feverish, body aches and pains, and fatigue)
AND
c. =1 moderate respiratory symptom (cough, sore throat and nasal congestion)
6. Onset of illness no more than 40 hours prior to randomization. Onset
of illness is defined as the time, the first of any one of the following,
occurred:
a. time when the subjects' temperature was measured as elevated (=
38.0 °C (=100.4 ºF)
OR
b. time when the subject first experienced at least one respiratory
symptom (cough, sore throat and nasal congestion)
OR
c. time when the subject first experienced at least one systemic
symptom (headache, feeling feverish, body aches and pains, and
fatigue)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 900
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Use of antiviral treatment for influenza (e.g. zanamivir, oseltamivir, rimantadine, or amantadine) within 14 days prior to screening
2. Received live attenuated or trivalent inactivated influenza virus
vaccine in the previous 3 weeks
3. History or presence of clinically significant pulmonary disease (e.g.,
chronic obstructive pulmonary disease, cystic fibrosis, or bronchiectasis)
or asthma
4. History of congestive heart failure with symptoms consistent with New York Heart Association Class III or IV functional status (See Appendix A: ) within the past 12 months
5. Presence of an immune compromised status due to chronic illness, organ transplantation or use of daily systemic immunosuppressants within 30 days prior to screening
6. Presence of clinically significant signs of acute respiratory distress during screening
7. Current use of inhaled medications (nasal or oral) or anticipated use of inhaled medications (nasal or oral) at any time during the study.
8. Current or a history of acute or chronic renal impairment requiring hemodialysis and/or a known calculated creatinine clearance (CLCR) of <60 mL/min
9. Presence of clinically significant abnormalities on ECG at screening which, in the investigator's clinical judgment, may affect either the subject's ability to participate in the study or the study results
10. History or presence of any clinical condition or evidence of organ dysfunction on examination which, in the opinion of the investigator, may affect either the subject's ability to participate in the study or the study results
11. Currently hospitalized or any planned hospitalizations within 1 month following the last dose of study drug
12. Current clinical evidence of otitis, bronchitis, sinusitis, pneumonia or active bacterial infection at any body site, that requires treatment with oral or parenteral antibiotics
13. Documented or reported (known) history of hepatitis B, hepatitis C, TB or HIV infection
14. Severe infection within 30 days prior to screening which required parenteral antibiotic use or hospitalization
15. History of or known clinically significant liver disease
16. History of, or current evidence of, abuse (in the investigator's opinion) of alcohol or any licit or illicit drug substance within the past 12 months
17. History of adverse reaction or known hypersensitivity to lactose or neuraminidase inhibitors
18. Received an investigational drug within 30 days prior to screening
19. Subjects who in the opinion of the investigator are unable to independently complete study documentation e.g. Flu-iiQ™ or selfadminister laninamivir octanoate TwinCaps® DPI


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Treatment of influenza caused by viruses type A and B
MedDRA version: 16.1 Level: LLT Classification code 10022002 Term: Influenza A virus infection System Organ Class: 100000004862
MedDRA version: 16.1 Level: LLT Classification code 10022003 Term: Influenza B virus infection System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Laninamivir octanoate TwinCaps® dry powder inhaler
Product Code: CS-8958
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: LANINAMIVIR OCTANOATE
Current Sponsor code: CS-8958
Other descriptive name: LANINAMIVIR OCTANOATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: The primary objective of the study is to evaluate the efficacy of two doses of inhaled laninamivir octanoate (40 and 80mg) delivered via TwinCaps® DPI in adults with symptomatic presumptive influenza A or B infection.

Timepoint(s) of evaluation of this end point: The time of symptom alleviation is defined as the period from start of study drug to the start of the first 24 hour period (three
consecutive measurements) in which the influenza symptoms are scored as mild or absent and fever is absent (<38.0°C/<100.4ºF).

Primary end point(s): The primary end point for this study is time to alleviation of influenza symptoms (cough, sore throat, nasal congestion, headache, body aches and pains, feeling feverish and fatigue) and fever for =24 hours.

Secondary Objective: -To evaluate the safety and tolerability of laninamivir octanoate
- To evaluate the incidence of secondary bacterial infections and the use of antibiotics
-To evaluate the efficacy of laninamivir octanoate
-To evaluate the quantitative changes in virus shedding
-To investigate the development of resistance to laninamivir by phenotypic and genotypic analyses
-To investigate the impact of treatment of influenza with laninamivir octanoate on quality of life

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Days 3, 5, 8, 15, and 29.

Secondary end point(s): - Time to return to body temperature of <37.2°C/99°F
- Time to alleviation of systemic symptoms
- Time to alleviation of respiratory symptoms
- Flu-iiQ symptom domain scores; systemic symptoms, respiratory
symptoms and all flu symptoms
- Area under the curve (AUC) of the duration and severity of the mean all
symptom score
- Determination of dose-response relationship in influenza infected
subjects
- Determination of the incidence of secondary bacterial infections and
the use antibiotics
- Incidence of SAEs, AEs leading treatment discontinuation, clinically significant changes in haematology, biochemistry and urinalysis laboratory tests
- Use of concomitant medications
- Changes on clinical assessments; vital signs, ECGs, physical examinations and spirometry
- Quantitative changes in virus shedding based on qRT-PCR and viral culture
- Determination of the emergence of resistance to laninamivir by phenotypic and genotypic analyses
- Quality of Life; impact on daily activities, impact on emotions and impact on others

Secondary ID(s)

BTA51-350-201

2013-000582-36-GB

Source(s) of Monetary Support

Biota Scientific Management Pty Ltd.

Biomedical Advanced Research and Development Authority, U.S. Department of Health and Human Services