Intramuscular Peramivir in Subjects With Uncomplicated Acute Influenza

• Sponsor: BioCryst Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00610935
• Collaborator: (none)
• Enrollment: 82
• Locations: 96
• Arms: 2
• Actual Duration (Months): 1
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and effectivess of a single intramuscular injection of peramivir for the treatment of subjects with acute, uncomplicated influenza.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: Peramivir; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intramuscular Peramivir in Subjects With Uncomplicated Acute Influenza.
• Actual Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo intramuscular injection	Drug: Placebo; Single intramuscular injection
Experimental: Peramivir Single intramuscular injection of 300mg peramivir	Drug: Peramivir; To evaluate the efficacy of peramivir administered intramuscularly compared to placebo on the time to alleviation of clinical symptoms in adult subjects with uncomplicated acute influenza.

Outcome Measures

Primary Outcome Measures

1. The Time to Alleviation of Clinical Signs and Symptoms of Influenza [Up to 14 days]

   The primary efficacy endpoint was the time to alleviation of symptoms of influenza in subjects diagnosed with influenza, defined as the time from injection of study drug to the start of the time period when a subject had Alleviation of Symptoms. A subject had Alleviation of Symptoms if each of the seven symptoms of influenza (cough, sore throat, nasal obstruction, myalgia [aches and pains], headache, feverishness, and fatigue) as self-assessed and recorded in the subject diary were either absent or were present at no more than mild severity level and at this status for at least 21.5 hours (24 hours minus 10%). No statistical testing was performed.

Secondary Outcome Measures

1. To Evaluate Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment. [Change from baseline assessed on days 3, 5 and 9.]

   The change in influenza viral titers was defined as the time-weighted change from Baseline in log_10 tissue culture infective dose_50 (TCID50/mL) and was summarized for each treatment group. The differences between the treatment groups were planned to be evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID50/mL were obtained at interval visits after treatment. As the study was terminated prematurely, no statistical testing was performed on these data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and non-pregnant female subjects age ≥18 years.

• A positive Influenza A and/or B Rapid Antigen Test (RAT) performed with a commercially available test kit on an adequate anterior nasal specimen, in accordance with the manufacturer's instructions. A negative initial RAT should be repeated within one-hour.

• Presence of fever at time of screening of ≥38.0 ºC (≥100.4 ºF) taken orally, or ≥38.5 ºC (≥101.2 ºF) taken rectally. A subject self-report of a history of fever or feverishness within the 24 hours prior to screening will also qualify for enrollment in the absence of documented fever at the time of screening.

• Presence of at least one respiratory symptom (cough, sore throat, or nasal symptoms) of at least moderate severity.

• Presence of at least one constitutional symptom (myalgia [aches and pains], headache, feverishness, or fatigue) of at least moderate severity.

• Onset of symptoms no more than 48 hours before presentation for screening.

• Written informed consent.

Exclusion Criteria:

• Women who are pregnant or breast-feeding.

• Presence of clinically significant signs of acute respiratory distress.

• History of severe chronic obstructive pulmonary disease (COPD) or severe persistent asthma (See section 15.2).

• History of congestive heart failure requiring daily pharmacotherapy with symptoms consistent with New York Heart Association Class III or IV functional status within the past 12 months.

• Screening ECG which suggests acute ischemia or presence of medically significant dysrhythmia.

• History of chronic renal impairment requiring hemodialysis and/or known or suspected to have moderate or severe renal impairment (actual or estimated creatinine clearance <50 mL/min).

• Clinical evidence of worsening of any chronic medical condition (temporally associated with the onset of symptoms of influenza) which, in the investigator's opinion, indicates that such finding(s) could represent complications of influenza.

• Current clinical evidence, including clinical signs and/or symptoms consistent with otitis, bronchitis, sinusitis and/or pneumonia, or active bacterial infection at any body site that requires therapy with oral or systemic antibiotics.

• Presence of immunocompromised status due to chronic illness, previous organ transplant, or use of immunosuppressive medical therapy which would include oral or systemic treatment with > 10 mg prednisone or equivalent on a daily basis within 30 days of screening.

• Currently receiving treatment for viral hepatitis B or viral hepatitis C.

• Presence of known HIV infection with a CD4 count <350 cell/mm3.

• Current therapy with oral warfarin or other systemic anticoagulant.

• Receipt of any doses of rimantadine, amantadine, zanamivir, or oseltamivir in the 7 days prior to screening.

• Immunized against influenza with live attenuated virus vaccine (FluMist®) in the previous 21 days.

• Immunized against influenza with inactivated virus vaccine within the previous 14 days.

• Receipt of any intramuscular injection within the previous 14 days.

• History of alcohol abuse or drug addiction within 1 year prior to admission in the study.

• Participation in a previous study of intramuscular or intravenous peramivir or previous participation in this study.

• Participation in a study of any investigational drug or device within the last 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Physical Express	Millbrook	Alabama	United States	36054
2	Alabama Family Medical Center	Tuscaloosa	Alabama	United States	35404
3	HOPE Research Institute	Phoenix	Arizona	United States	85050
4	Clopton Clinic	Jonesboro	Arkansas	United States	72401
5	Research Solutions, LLC	Jonesboro	Arkansas	United States	72401
6	Kevin Adkins, MD	Mountain Home	Arkansas	United States	72653
7	NuLife Clinical Research, Inc.	Anaheim	California	United States	92805
8	Impact Clinical Trials	Beverly Hills	California	United States	90211
9	Associated Pharmaceutical Research Center, Inc.	Buena Park	California	United States	90620
10	Med Investigations Incorporated	Fair Oaks	California	United States	95628
11	Universal Biopharma Research Institute Inc.	Fresno	California	United States	93703
12	Research Center of Fresno, Inc	Fresno	California	United States	93726
13	Harmony Clinical, Inc.	Garden Grove	California	United States	92843
14	Allergy, Asthma, and Respiratory Care Medical Center	Long Beach	California	United States	90806
15	National Institute of Clinical Research	Los Angeles	California	United States	90017
16	Center for Clinical Trials, LLC	Paramount	California	United States	90723
17	San Diego Sports Medicine and Family Health Center	San Diego	California	United States	92120
18	Coastal Medical Research Group, Inc.	San Luis Obispo	California	United States	93405
19	Alpine Clinical Research Center	Boulder	Colorado	United States	80304
20	Clinicos, LLC	Colorado Springs	Colorado	United States	80904
21	Longmont Clinic, P.C.	Longmont	Colorado	United States	80501
22	Florida Research Network, LLC	Gainesville	Florida	United States	32605
23	AGA Clinical Trials	Hialeah	Florida	United States	33012
24	Eastern Research	Hialeah	Florida	United States	33013
25	Century Clinical Research Inc	Holly Hill	Florida	United States	32117
26	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32205
27	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
28	Office of Roger J. Miller, Jr., MD	Jacksonville	Florida	United States	32257
29	MD Now Medical Center	Lake Worth	Florida	United States	33463
30	DMI Healthcare Group	Largo	Florida	United States	33773
31	Well Pharma Medical Research, Corp.	Miami	Florida	United States	33143
32	Compass Research LLC	Orlando	Florida	United States	32806
33	Pines Research, LLC	Pembroke Pines	Florida	United States	33028
34	Wilker/Powers Center for Clinical Studies	Saint Cloud	Florida	United States	34769
35	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
36	Sandersville Family Practice Center	Sandersville	Georgia	United States	31082
37	Quincy Medical Group	Quincy	Illinois	United States	62301
38	Investigators Research Group, LLC	Indianapolis	Indiana	United States	46268
39	Welborn Clinic Gateway	Newburgh	Indiana	United States	47630
40	Medical Associates Clinic PC	Dubuque	Iowa	United States	52001
41	Heart of America Research Institute	Shawnee Mission	Kansas	United States	66216
42	American Medical Exams, P.A.	Topeka	Kansas	United States	66608
43	Heartland Research Associates, LLC	Wichita	Kansas	United States	67212
44	Kentucky Lung Clinic	Hazard	Kentucky	United States	41701
45	Winchester, Patton, Burgess, PSC	Whitley City	Kentucky	United States	42653-0099
46	Gulf Coast Research, LLC	Baton Rouge	Louisiana	United States	70808
47	Gulf Coast Research LLC	Lafayette	Louisiana	United States	70503
48	Byron Jackson	Shreveport	Louisiana	United States	71104
49	Professional Clinical Research-Benzonia	Benzonia	Michigan	United States	49616
50	Professional Clinical Research, Inc.	Cadillac	Michigan	United States	49601
51	Professional Clinical Research-Interlochen	Interlochen	Michigan	United States	49643
52	KMED Research	Saint Clair Shores	Michigan	United States	48081
53	Olive Branch Family Medical Center	Olive Branch	Mississippi	United States	38654
54	Clinvest	Springfield	Missouri	United States	65807
55	Clinical Research Department	Bozeman	Montana	United States	59715
56	Mercury Street Medical Group, PLLC	Butte	Montana	United States	59701
57	Prarie Fields Family Medicine, P.C	Fremont	Nebraska	United States	68025
58	Quick Care Medical	Hamilton	New Jersey	United States	08690
59	Health Sciences Research Center at Asthma & Allergy Associates P.C.	Elmira	New York	United States	14901
60	Health Sciences Research Center	Ithaca	New York	United States	14850
61	American Institute of Healthcare & Fitness	Raleigh	North Carolina	United States	27605
62	Community Medical Partners	Canfield	Ohio	United States	44406
63	Parsons Avenue Medical Clinic	Columbus	Ohio	United States	43207
64	Ohio Clinical Research LLC	Lyndhurst	Ohio	United States	44124
65	Physician Care PM	Edmond	Oklahoma	United States	73013
66	Urgent Care of Green County	Owasso	Oklahoma	United States	74055
67	Integrated Medical Research PC	Ashland	Oregon	United States	97520
68	Primary Physicians Research Inc.	Pittsburgh	Pennsylvania	United States	15241
69	Warminster Medical Associates, PC	Warminster	Pennsylvania	United States	18974
70	New England Center for Clinical Research, Inc.	Cranston	Rhode Island	United States	02920
71	Clinical Partners, LLC	Johnston	Rhode Island	United States	02919
72	Paris View Family Practice	Greenville	South Carolina	United States	29601
73	Andras Koser	Greenville	South Carolina	United States	29615
74	Hillcrest Clinical Research, LLC	Simpsonville	South Carolina	United States	29681
75	S. Carolina Pharmaceutical Research	Spartanburg	South Carolina	United States	29303
76	Holston Medical Group, PC	Bristol	Tennessee	United States	37620
77	Holston Medical Group, P.C.	Kingsport	Tennessee	United States	37660
78	DiscoveResearch Inc.	Beaumont	Texas	United States	77701
79	DiscoveResearch, Inc.	Bryan	Texas	United States	77802
80	Intrinsic Research Data, Inc.	Corpus Christi	Texas	United States	78411
81	Allergy/Immunology Research Center of North Texas	Dallas	Texas	United States	75230
82	Research Across America	Dallas	Texas	United States	75234
83	West Houston Clinical Research Service	Houston	Texas	United States	77055
84	Dynamed Clinical Research, L.P.	Houston	Texas	United States	77070
85	Sun Research Institute	San Antonio	Texas	United States	78205
86	GSA Research	San Antonio	Texas	United States	78213
87	San Antonio Preventive and Diagnostic Medicine	San Antonio	Texas	United States	78229
88	Optimum Clinical Research	Salt Lake City	Utah	United States	84102
89	J. Lewis Research Inc	Salt Lake City	Utah	United States	84109
90	J. Lewis Research Inc. Foothill Family Clinic South	Salt Lake City	Utah	United States	84121
91	J. Lewis Research, Inc.	Salt Lake City	Utah	United States	84121
92	Physicians Research Options, LLC	Saratoga Springs	Utah	United States	84045
93	J. Lewis Research Inc. FirstMed	West Jordan	Utah	United States	84088
94	Virginia Adult & Pediatric Allergy & Asthma, P.C Department of Clinical Research	Richmond	Virginia	United States	23229
95	Holston Medical Group	Weber City	Virginia	United States	24290
96	Northwest Clinical Research Center	Bellevue	Washington	United States	98004

Sponsors and Collaborators

• BioCryst Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 24, 2007

More Information

Publications

None provided.

• Responsible Party: BioCryst Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00610935
• Other Study ID Numbers: BCX1812 311; HHS # O100200700032C
• First Posted: Feb 8, 2008
• Last Update Posted: Mar 17, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by BioCryst Pharmaceuticals: Influenza; Subjects with uncomplicated acute influenza
• Additional relevant MeSH terms: Influenza, Human; Peramivir

Study Results

Participant Flow

Pre-assignment Detail	Subjects were centrally randomized in a ratio of 2:1 to a single dose of IM peramivir 300 mg or placebo, in accordance with a computer-generated randomization schedule prepared by a non-study statistician. Each subject's assignment to treatment was stratified according to smoking status and RAT test for influenza A or B.

Arm/Group Title	Placebo	Peramivir
Arm/Group Description	Placebo intramuscular injection	Single intramuscular injection of 300mg peramivir
Period Title: Overall Study
STARTED	25	57
ITTI Population	25	55
ITT Population	25	57
COMPLETED	24	54
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Placebo	Peramivir	Total
Arm/Group Description	Placebo intramuscular injection	Single intramuscular injection of 300mg peramivir	Total of all reporting groups
Overall Participants	25	57	82
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.9 (8.86)	32.6 (12.67)	33.0 (11.60)
Sex: Female, Male (Count of Participants)
Female	14 56%	28 49.1%	42 51.2%
Male	11 44%	29 50.9%	40 48.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 8%	2 3.5%	4 4.9%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.8%	1 1.2%
Black or African American	2 8%	4 7%	6 7.3%
White	15 60%	41 71.9%	56 68.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 24%	9 15.8%	15 18.3%
Current Smoking Behavior at Randomization (participants) [Number]
Smoker	4 16%	14 24.6%	18 22%
Non-smoker	21 84%	43 75.4%	64 78%
Influenza PCR Results (participants) [Number]
Negative	0 0%	2 3.5%	2 2.4%
Influenza A (H1N1)	5 20%	16 28.1%	21 25.6%
Influenza A (H3N2)	15 60%	33 57.9%	48 58.5%
Influenza A (IND)	1 4%	0 0%	1 1.2%
Influenza B	4 16%	6 10.5%	10 12.2%
Influenza A and B	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	The Time to Alleviation of Clinical Signs and Symptoms of Influenza
Description	The primary efficacy endpoint was the time to alleviation of symptoms of influenza in subjects diagnosed with influenza, defined as the time from injection of study drug to the start of the time period when a subject had Alleviation of Symptoms. A subject had Alleviation of Symptoms if each of the seven symptoms of influenza (cough, sore throat, nasal obstruction, myalgia [aches and pains], headache, feverishness, and fatigue) as self-assessed and recorded in the subject diary were either absent or were present at no more than mild severity level and at this status for at least 21.5 hours (24 hours minus 10%). No statistical testing was performed.
Time Frame	Up to 14 days

Outcome Measure Data

Analysis Population Description

A total of 80 subjects met the criteria for inclusion in the ITTI population as defined by a positive PCR assay for influenza A or B from the nasopharyngeal specimen obtained prior to administration of study treatment. Seventy-nine of these were included in the primary efficacy analysis for whom data for time to symptom alleviation were available; There was insufficient data from one subject in the placebo group to enable determination of the Time to Alleviation of Symptoms.

Arm/Group Title	Placebo	Peramivir
Arm/Group Description	Placebo intramuscular injection	Single intramuscular injection of 300mg peramivir
Measure Participants	24	55
Median (95% Confidence Interval) [hours]	118.3	103.9

2. Secondary Outcome

Title	To Evaluate Changes in Influenza Virus Titer in Nasopharyngeal Samples in Response to Treatment.
Description	The change in influenza viral titers was defined as the time-weighted change from Baseline in log_10 tissue culture infective dose_50 (TCID50/mL) and was summarized for each treatment group. The differences between the treatment groups were planned to be evaluated using a Wilcoxon Rank Sum Test controlling for current smoking behavior. Specimens for virologic culture and determination of influenza virus TCID50/mL were obtained at interval visits after treatment. As the study was terminated prematurely, no statistical testing was performed on these data.
Time Frame	Change from baseline assessed on days 3, 5 and 9.

Outcome Measure Data

Analysis Population Description

The Intent To Treat Infected population (ITTI) population included all subjects who were randomized, received study drug, and had confirmed influenza A and/or B by primary viral culture or PCR.

Arm/Group Title	Placebo	Peramivir
Arm/Group Description	Placebo intramuscular injection	Single intramuscular injection of 300mg peramivir
Measure Participants	20	49
Baseline	3.75	3.75
Day 3 - Change from baseline	-2.25	-2.75
Day 5 - Change from baseline	-3.00	-3.00
Day 9 - Change from baseline	-3.00	-3.25

Adverse Events

Time Frame	Reports of TEAEs were collected from the time of study drug administration through to the follow-up period ending on Day 14.
Arm/Group Title	Placebo		Peramivir
Arm/Group Description	Placebo intramuscular injection		Single intramuscular injection of 300mg peramivir
All Cause Mortality
	Placebo		Peramivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/57 (0%)
Serious Adverse Events
	Placebo		Peramivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Peramivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/25 (52%)		26/57 (45.6%)
Gastrointestinal disorders
Diarrhea	1/25 (4%)	1	4/57 (7%)	4
Nausea	2/25 (8%)	2	4/57 (7%)	4
Vomiting	3/25 (12%)	3	4/57 (7%)	4
General disorders
Injection Site Pain	1/25 (4%)	1	4/57 (7%)	4
Investigations
Urine Protein Present	1/25 (4%)	1	1/57 (1.8%)	1
Musculoskeletal and connective tissue disorders
Myalgia	0/25 (0%)	0	3/57 (5.3%)	3
Muscle Spasms	1/25 (4%)	1	1/57 (1.8%)	1
Nervous system disorders
Ageusia	0/25 (0%)	0	2/57 (3.5%)	2
Dizziness	1/25 (4%)	1	4/57 (7%)	4
Syncope Vasovagal	3/25 (12%)	3	0/57 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/25 (0%)	0	2/57 (3.5%)	2

Limitations/Caveats

The study was terminated at the discretion of the Sponsor after 82 of the planned 600 subjects were enrolled. The reason for study termination was to allow the Sponsor to focus development efforts on a more concentrated formulation which would also allow evaluation of higher doses of peramivir administered intramuscularly.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.