FROSTY: Safety & Pharmacokinetics Study of Inhaled Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Children With Influenza

Sponsor

Biota Scientific Management Pty Ltd (Industry)

Overall Status

Terminated

CT.gov ID

NCT02014649

Collaborator

Department of Health and Human Services (U.S. Fed)

Enrollment

Locations

Arms

5.9

Duration (Months)

0.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase 1/2 protocol is designed to collect safety, tolerability and pharmacokinetic data of two doses of Laninamivir Octanoate in children and adolescents. The protocol will also explore virology and efficacy endpoints.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: 20 mg laninamivir octanoate Drug: Placebo Drug: 40 mg laninamivir octanoate	Phase 1/Phase 2

Detailed Description

Approximately 48 subjects aged 5-17 years inclusive will be randomised into the study.

Subjects with recent onset of presumptive influenza will have influenza A or B infection confirm by Rapid Antigen Test.

The study will be conducted on an outpatient basis. The dose is administered in a single session in the clinic on Day 1. The subject will return to the clinic for assessments and follow up.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Randomised, Parallel Dose, Phase 1/2 Safety and Pharmacokinetics Study of Inhaled Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Children With Naturally Acquired Influenza A or B

Study Start Date :

Nov 1, 2013

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 20mg Laninamivir Octanoate Dry Powder plus placebo	Drug: 20 mg laninamivir octanoate Other Names: CS-8958 Drug: Placebo Other Names: Lactose
Experimental: 40mg Laninamivir Octanoate Dry Powder	Drug: 40 mg laninamivir octanoate Other Names: CS-8958

Arm

Intervention/Treatment

Experimental: 20mg Laninamivir Octanoate

Dry Powder plus placebo

Drug: 20 mg laninamivir octanoate

Other Names:

CS-8958

Drug: Placebo

Other Names:

Lactose

Experimental: 40mg Laninamivir Octanoate

Dry Powder

Drug: 40 mg laninamivir octanoate

Other Names:

CS-8958

Outcome Measures

Primary Outcome Measures

To evaluate the safety and tolerability of laninamivir octanoate following administration of the dose by inhalation in children with influenza A or B infection [Subjects are assessed at clinic visits and followed up to 28-days post dose.]
Safety data will be presented according to dose group and age strata. All safety data will be summarized with descriptive statistics, and include assessment of SAEs, AEs, Clinically Significant changes in routine labs, O2 Saturation, ECG, Vitals, Con Meds, Physical Exam findings.

Secondary Outcome Measures

To evaluate the pharmacokinetic (PK) profiles of the prodrug, laninamivir octanoate, and its active metabolite, laninamivir, following administration of a single dose (20 or 40 mg) [Samples are collected at clinic visits over 5 days.]
Pharmacokinetic parameters will be calculated and summarized, PK concentration data will add to population models.

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects' parent/legally acceptable representative/guardian must give written informed consent to participate in the study and must understand the nature of the study and must be willing to comply with all protocol requirements. Subjects over 12 must provide assent to participate in the study and potential subjects below this age should provide assent if deemed appropriate to the maturity level of the subject or if required according to local guidance/regulations.
Males or females aged between 5 and 17 years inclusive, who weigh at least 15 kg at screening.
Confirmed influenza infection based on positive rapid antigen test (RAT) for Influenza A or B.
Fever, defined as either:

Otic temperature ≥38.0° C (100.4°F) at the screening visit, OR,
A history of fever within the 24 hours prior to the screening visit and has administered antipyretic(s) in the 6 hours prior to the screening visit.

Presence on the Screening questionnaire of, at least two, of the following influenza symptoms:

Non-productive Cough, of at least moderate severity,
Sore throat, of at least moderate severity,
Nasal congestion/runny nose, of at least moderate severity,
Headache, of at least moderate severity,
Muscle aches and pain, of at least moderate severity,
Feeling feverish, of at least moderate severity,
Low energy, tired, fatigue, of at least moderate severity;

Onset of illness no more than 40 hours before randomization, defined as:

time when the temperature was first measured as elevated ≥38.0°C (oral or otic) OR
time when the subject first experienced at least one influenza symptom (non-productive cough, sore throat or nasal congestion/runny nose, headache, muscle aches and pain, feeling feverish, or low energy/tired/fatigue)

In the Investigator's opinion able to complete the required inhalations of the investigational medicinal product.

Exclusion Criteria:

Use of antiviral treatment for influenza (e.g., zanamivir, oseltamivir, peramivir, rimantadine, or amantadine) within 14 days prior to screening
Received influenza virus vaccine in the previous 3 weeks.
History or presence of clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, cystic fibrosis, or bronchiectasis)
Current asthma requiring treatment, or history of asthma requiring treatment in the last 5 years, or episode of wheezing in the 12 months prior to randomization.
History of congestive heart failure with symptoms consistent with New York Heart Association Class III or IV functional status.
Presence of an immune compromised status due to chronic illness, organ transplantation or use of daily systemic immunosuppressants
Presence of clinically significant signs of acute respiratory distress during screening.
Current use of inhaled medications (nasal or oral) or anticipated use of inhaled medications (nasal or oral) at any time during the study.
Current or a history of acute or chronic renal impairment/disease
Currently hospitalized or any planned hospitalizations within 1 month following the last dose of IMP.
Current clinical evidence of otitis, bronchitis, sinusitis, or pneumonia or active bacterial infection at any body site
Severe infection within 30 days prior to screening which required parenteral antibiotic use or hospitalization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Precision Trials LLC	Phoenix	Arizona	United States	85032
2	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
3	SoCal Clinical Research Med Group	Bellflower	California	United States	90706
4	Sherif Khamis MD Inc	Canoga Park	California	United States	91306
5	Advanced Medical Research	Lakewood	California	United States	90712
6	Madera Family Medical Group	Madera	California	United States	93637
7	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
8	A.G.A Clinical Trials	Hialeah	Florida	United States	33012
9	Lafayette Clinical Research Group	Lafayette	Indiana	United States	47905
10	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
11	Louisiana State University Health Sciences Center	Shreveport	Louisiana	United States	71103
12	Dr Haidar's Clinic	Carriere	Mississippi	United States	39426
13	DePaul Health Center	Bridgeton	Missouri	United States	63044
14	Blue Ridge Pediatric and Adolescent Medicine Group	Boone	North Carolina	United States	28607
15	Dayton Children's Hospital	Dayton	Ohio	United States	45404
16	The University of Toledo Medical Center	Toledo	Ohio	United States	43606
17	Dr Santiago Reyes	Oklahoma	Oklahoma	United States	73112
18	Cyn3rgy Research	Gresham	Oregon	United States	97030
19	Sanford Research University of South Dakota	Sioux Falls	South Dakota	United States	57117
20	Avant Research Assoc.	Houston	Texas	United States	77052
21	West Houston Clinical Research Service	Houston	Texas	United States	77055
22	Foothill Family Clinic	Salt Lake City	Utah	United States	84109
23	First Med	Salt Lake City	Utah	United States	84121
24	Foothill Family Clinic South	Salt Lake City	Utah	United States	84121
25	Copperview Medical Center	South Jordan	Utah	United States	84095
26	Dixie Pediatrics	St. George	Utah	United States	84790
27	Rockwood Clinic	Spokane	Washington	United States	99202
28	Rockwood North Clinic	Spokane	Washington	United States	99218