Xofluza Drug Information
Generic name: BALOXAVIR MARBOXIL
Uses of Xofluza
Treatment of Influenza XOFLUZA is indicated for treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications 1.
Post-Exposure Prophylaxis of Influenza XOFLUZA is indicated for post-exposure prophylaxis of influenza in persons 5 years of age and older following contact with an individual who has influenza.
Limitations of Use
Influenza viruses change over time, and factors such as the virus type or subtype, emergence of resistance, or changes in viral virulence could diminish the clinical benefit of antiviral drugs. Consider available information on drug susceptibility patterns for circulating influenza virus strains when deciding whether to use XOFLUZA.
Dosage & Administration of Xofluza
Dosage and Administration Overview XOFLUZA is available in two dosage forms: XOFLUZA tablets (40 mg and 80 mg). XOFLUZA for oral suspension is available in two different presentations: packets (30 mg and 40 mg) and bottles (2 mg/mL). If the patient weighs less than 15 kg, XOFLUZA for oral suspension in bottle is the recommended presentation.
Both presentations of the for oral suspension are intended for patients who are unable to or have difficulty swallowing tablets, or those who require enteral administration. Take XOFLUZA as soon as possible after influenza symptom onset or exposure to influenza. XOFLUZA may be taken with or without food.
However, concomitant use of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc) should be avoided.
Recommended Dosage Treatment of Acute Uncomplicated Influenza or Post-Exposure Prophylaxis in Adults, and Pediatric Patients (5 Years of Age and Older) Take XOFLUZA as a single dose as soon as possible and within 48 hours of influenza symptom onset for treatment of acute uncomplicated influenza or following contact with an individual who has influenza. Table 1 XOFLUZA Tablets: Recommended Dosage in Adults and Pediatric Patients 5 Years of Age and Older Table 2 XOFLUZA for Oral Suspension (Packets): Recommended Dosage in Adults and Pediatric Patients 5 Years of Age and Older Table 3 XOFLUZA for Oral Suspension (Bottles): Recommended Dosage in Adults and Pediatric Patients 5 Years of Age and Older
Preparation of XOFLUZA for Oral Suspension (Packets) by Patient or Caregiver See the XOFLUZA for oral suspension (packets) Instructions for Use for details on the preparation and administration (oral or via enteral feeding tube). Once the supplied XOFLUZA for oral suspension (packets) have fully dispersed in the drinking water, take the entire mixture immediately. For the 80 mg dose, use two 40 mg packets.
Prepare each packet as described above for the 40 mg dose and take the packets separately. For enteral administration (i.e., feeding tube), draw up the entire contents with an enteral syringe and administer through a tube that is 4 French or larger. Flush with 1 mL of water before and after enteral administration.
Preparation of XOFLUZA for Oral Suspension (Bottles) by Healthcare Provider Prior to dispensing to the patient, reconstitute XOFLUZA for oral suspension (bottles) with 20 mL of drinking water or sterile water. After reconstitution, each bottle of XOFLUZA for oral suspension (bottles) contains 40 mg of baloxavir marboxil per 20 mL of volume for a final concentration of 2 mg/mL. The for oral suspension (bottles) can be used for oral or enteral use.
Only take the contents of the full bottle(s) of XOFLUZA for oral suspension (bottles) with the use of a measuring device (oral syringe). Ensure the caregiver or patient uses an oral syringe to measure the prescribed dose of XOFLUZA for oral suspension (bottles). Patients may need to draw up XOFLUZA for oral suspension (bottles) multiple times using the oral syringe to receive the full dose.
Reconstituting XOFLUZA for Oral Suspension (Bottles) Prepare the for oral suspension (bottles) at the time of dispensing. Administration must occur within 10 hours after reconstitution because this product does not contain a preservative. Gently tap the bottom of the bottle to loosen the granules.
Gently swirl the suspension to ensure that the granules are evenly suspended. Do not shake. Write the expiration time and date on the bottle label in the space provided (10 hours from reconstitution time).
Important Information for the Healthcare Provider Provide caregiver or patient with a measuring device (oral syringe) to deliver the prescribed dose of the for suspension for oral use (bottles). For enteral administration (i.e., feeding tube), draw up for oral suspension (bottles) with an enteral syringe and administer through a tube that is 4 French or larger. Instruct the caregiver or patient that the total prescribed dose of XOFLUZA for oral suspension (bottles) may require: Less than one bottle (e.g., for pediatric patients 5 years of age and older who weigh less than 20 kg) One bottle (e.g., for adults and adolescents weighing 20 kg to less than 80 kg), or Two bottles (e.g., for adults and adolescents weighing at least 80 kg).
| Patient Body Weight | Recommended Single Oral Dose in Patients 5 Years of Age and Older (Tablets) |
|---|---|
| 20 kg to less than 80 kg | One 40 mg tablet (blister card contains one 40 mg tablet) |
| At least 80 kg | One 80 mg tablet (blister card contains one 80 mg tablet) |
| Patient Body Weight | Recommended Single Oral Dose in Patients 5 Years of Age and Older For Oral Suspension (Packets) |
|---|---|
| 15 kg to less than 20 kg | One 30 mg packet |
| 20 kg to less than 80 kg | One 40 mg packet |
| At least 80 kg | 80 mg (two 40 mg packets) |
| Patient Body Weight | Recommended Single Oral Dose in Patients 5 Years of Age and Older For Oral Suspension (Bottles) |
|---|---|
| Less than 20 kg | 2 mg/kg |
| 20 kg to less than 80 kg | 40 mg (20 mL) |
| At least 80 kg | 80 mg (40 mL) |
| Patient Body Weight | Recommended Single Oral Dose (Tablets) Recommended XOFLUZA dosage is based on the patient's weight. |
|---|---|
| 20 kg to less than 80 kg | One 40 mg tablet (blister card contains one 40 mg tablet) |
| At least 80 kg | One 80 mg tablet (blister card contains one 80 mg tablet) |
| Patient Body Weight | Recommended Single Oral Dose (Packets) Recommended XOFLUZA dosage is based on the patient's weight. |
|---|---|
| 15 kg Patients who weigh less than 15 kg should receive XOFLUZA for oral suspension (bottles). to less than 20 kg | One 30 mg packet |
| 20 kg to less than 80 kg | One 40 mg packet |
| At least 80 kg | 80 mg (two 40 mg packets) |
| Patient Body Weight | Recommended Single Oral Dose Recommended XOFLUZA dosage is based on the patient's weight., Use a measuring device (oral syringe) to measure the prescribed dose for use. (For Oral Suspension in Bottles) |
|---|---|
| Less than 20 kg | 2 mg/kg |
| 20 kg to less than 80 kg | 40 mg (20 mL) |
| At least 80 kg | 80 mg (40 mL Dosage requires two bottles of XOFLUZA for oral suspension. ) |
Side Effects of Xofluza
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The overall safety profile of XOFLUZA is based on data from 2,079 subjects, 5 years of age and older in 5 controlled clinical trials who received XOFLUZA. These trials included otherwise healthy adults and adolescents (N=910) and subjects at high risk of developing complications associated with influenza (N=730).
Of these, 1,440 subjects received XOFLUZA at the recommended dose. Trial T0821 was a phase 2 dose-finding placebo-controlled trial where otherwise healthy adult subjects 20 to 64 years of age received single oral dose of XOFLUZA or placebo. Trial T0831 was a placebo- and active-controlled trial in otherwise healthy adults and adolescents 12 to 64 years of age; subjects received weight-based XOFLUZA or placebo as a single oral dose on Day 1 or oseltamivir twice a day for 5 days.
Trial T0832 was a randomized, double-blind, placebo- and active-controlled trial where adults and adolescents at high risk of influenza complications 12 years of age and older received either XOFLUZA, placebo or oseltamivir. Table 4 displays the most common adverse events (regardless of causality assessment) reported in at least 1% of adult and adolescent subjects who received XOFLUZA at the recommended dose in Trials T0821, T0831, and T0832. Table 4 Incidence of Adverse Events Occurring in at Least 1% of Adult and Adolescent Subjects Receiving XOFLUZA in the Acute Uncomplicated Influenza Trials T0821, T0831, and T0832 Pediatric Subjects (5 to < 12 Years of Age): In an active-controlled, double-blind trial Trial CP40563 in pediatric subjects, a total of 79 subjects 5 to less than 12 years of age, received the recommended weight-based dosage of XOFLUZA, and 39 subjects received oseltamivir.
The most frequently reported AEs (≥ 5%) in all subjects in the XOFLUZA treatment arm were vomiting (5%) and diarrhea (5%). Vomiting was reported in 18% of subjects in the oseltamivir arm. There are limited safety data in patients 5 to <12 years at high risk of developing influenza complications.
The safety profile was similar in pediatric patients aged 5 to < 12 years old as that reported in adults and adolescents 12 years of age and older.
Postmarketing Experience
The following adverse reactions have been identified during postmarketing use of XOFLUZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to XOFLUZA exposure. Immune System Disorders: Anaphylactic reactions, anaphylactic shock, anaphylactoid reactions, hypersensitivity reactions, angioedema (swelling of face, eyelids, tongue and lips) Skin and Subcutaneous Tissue Disorders: Rash, urticaria, erythema multiforme Gastrointestinal Disorders: Vomiting, hematochezia, melena, colitis Psychiatric Disorders: Delirium, abnormal behavior, hallucinations
| Adverse Event | XOFLUZA (N=1,440) | Placebo (N=1,136) |
|---|---|---|
| Diarrhea | 3% | 4% |
| Bronchitis | 3% | 4% |
| Nausea | 2% | 3% |
| Sinusitis | 2% | 3% |
| Headache | 1% | 1% |
Warnings & Cautions for Xofluza
Hypersensitivity Cases of anaphylaxis, urticaria, angioedema, and erythema multiforme have been reported in postmarketing experience with XOFLUZA. Appropriate treatment should be instituted if an allergic-like reaction occurs or is suspected. The use of XOFLUZA is contraindicated in patients with known hypersensitivity to XOFLUZA.
Increased Incidence of Treatment-Emergent Resistance in Patients Less Than 5 Years of Age XOFLUZA is not indicated in patients less than 5 years of age due to increased incidence of treatment-emergent resistance in this age group. The potential for transmission of resistant strains in the community has not been determined.
Risk of Bacterial Infections There is no evidence of efficacy of XOFLUZA in any illness caused by pathogens other than influenza viruses. Serious bacterial infections may begin with influenza-like symptoms or may coexist with, or occur as, a complication of influenza. XOFLUZA has not been shown to prevent such complications.
Prescribers should be alert to potential secondary bacterial infections and treat them as appropriate.
Drug Interactions with Xofluza
Effect of Other Drugs on XOFLUZA Baloxavir may form a chelate with polyvalent cations such as calcium, aluminum, or magnesium. Coadministration with polyvalent cation-containing products may decrease plasma concentrations of baloxavir, which may reduce XOFLUZA efficacy. Avoid coadministration of XOFLUZA with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).
Vaccines
The concurrent use of XOFLUZA with intranasal live attenuated influenza vaccine (LAIV) has not been evaluated. Concurrent administration of antiviral drugs may inhibit viral replication of LAIV and thereby decrease the effectiveness of LAIV vaccination. Interactions between inactivated influenza vaccines and XOFLUZA have not been evaluated.
Pregnancy Safety for Xofluza
Pregnancy Risk Summary There are no adequate and well-controlled studies with XOFLUZA in pregnant women to inform a drug-associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with influenza virus infection in pregnancy (see Clinical Considerations ). In animal reproduction studies, no adverse developmental effects were observed in rats or rabbits with oral administration of baloxavir marboxil at exposures approximately 5 (rats) and 7 (rabbits) times the systemic baloxavir exposure at the maximum recommended human dose (MRHD) (see Data ).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes, including maternal death, stillbirth, birth defects, preterm delivery, low birth weight, and small for gestational age. No adverse embryo-fetal effects were observed in rats up to the highest dose of baloxavir marboxil (1,000 mg/kg/day), resulting in systemic baloxavir exposure (AUC) of approximately 5 times the exposure at the MRHD. In rabbits, fetal skeletal variations occurred at a maternally toxic dose (1,000 mg/kg/day) resulting in 2 abortions out of 19 pregnancies.
No adverse maternal or embryo-fetal effects were observed in rabbits at the middle dose (100 mg/kg/day) resulting in systemic baloxavir exposure (AUC) approximately 7 times the exposure at the MRHD. No significant effects were observed in the offspring at maternal systemic baloxavir exposure (AUC) approximately 5 times the exposure at the MRHD.
Pediatric Use of Xofluza
Pediatric Use Treatment of Acute Uncomplicated Influenza in Adolescent Subjects (≥ 12 Years of Age) The safety and effectiveness of XOFLUZA for the treatment of acute uncomplicated influenza in adolescent subjects 12 years of age and older weighing at least 40 kg is supported by one randomized, double-blind, controlled trial in otherwise healthy subjects Trial T0831 and one trial in subjects at high risk of developing influenza-related complications Trial T0832. A total of 117 otherwise healthy adolescents 12 to17 years of age were randomized and received either XOFLUZA (N=76) or placebo (N=41) in Trial T0831; 38 adolescents 12 to 17 years of age at high risk for influenza complications were randomized and received either XOFLUZA (N=21) or placebo (N=17) in Trial T0832. The median time to alleviation of symptoms in influenza-infected adolescent subjects aged 12 to 17 years in Trial T0831 was comparable to that observed in adults.
In Trial T0832, the median time to improvement of symptoms in the limited number of influenza-infected adolescent subjects aged 12 to 17 years was similar in the XOFLUZA and placebo arms. Adverse events reported in adolescents in both trials were similar to those reported in adults. Treatment of Acute Uncomplicated Influenza in Pediatric Subjects (5 to < 12 Years of Age) The safety and effectiveness of XOFLUZA in pediatric subjects 5 to less than 12 years of age is supported by one randomized, double-blind, controlled trial Trial CP40563 with a primary endpoint of safety.
In this trial, 118 pediatric subjects were randomized and treated in a 2:1 ratio and received either XOFLUZA (N=79) or oseltamivir (N=39). Efficacy was extrapolated from adults and adolescents based on comparable PK exposures in adults, adolescents and pediatric subjects 5 to less than 12 years of age. The median time to alleviation of signs and symptoms in influenza-infected subjects was comparable in the XOFLUZA and oseltamivir arms.
Post-Exposure Prophylaxis of Influenza in Pediatric and Adolescent Subjects (5 to < 18 Years of Age) The safety and effectiveness of XOFLUZA for post-exposure prophylaxis in pediatric and adolescent subjects 5 to less than 18 years of age is supported by one randomized, double-blind, controlled trial conducted in Japan Trial T0834. Subjects in this trial were randomized in a 1:1 ratio to receive XOFLUZA or placebo. A total of 69 subjects from 5 to <18 years of age in Trial T0834 received XOFLUZA.
The incidence of RT-PCR-confirmed symptomatic influenza in pediatric subjects 5 to <18 years of age was similar to that observed in adult subjects. Adverse events reported in pediatric and adolescent subjects were similar to those reported in adults in the same trial. Pediatric Subjects (< 5 Years of Age) The safety and effectiveness of XOFLUZA for treatment and post-exposure prophylaxis of influenza in pediatric subjects less than 5 years of age, including neonates, have not been established.
Contraindications for Xofluza
XOFLUZA is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil or any of its ingredients. Serious allergic reactions have included anaphylaxis, angioedema, urticaria, and erythema multiforme.
Overdosage Information for Xofluza
Treatment of an overdose of XOFLUZA should consist of general supportive measures, including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with XOFLUZA. Baloxavir is unlikely to be significantly removed by dialysis due to high serum protein binding.
Clinical Studies of Xofluza
Treatment of Acute Uncomplicated Influenza—Otherwise Healthy Subjects (12 Years of Age and Older) Two randomized, controlled, double-blinded clinical trials conducted in two different influenza seasons evaluated efficacy and safety of XOFLUZA in otherwise healthy subjects with acute uncomplicated influenza. All subjects in Trial T0821 were Asian, the majority of subjects were male (62%), and the mean age was 38 years. In this trial, among subjects who received XOFLUZA and had influenza virus typed, influenza A/H1N1 was the predominant strain (63%), followed by influenza B (25%), and influenza A/H3N2 (12%).
In Trial T0831 (NCT02954354), a phase 3, randomized, double-blind, active- and placebo-controlled trial, XOFLUZA was studied in 1,436 otherwise healthy adults and adolescents with signs and symptoms of influenza in the U.S. and Japan. Subjects were 12 to 64 years of age and weighed at least 40 kg. Subjects in the XOFLUZA and placebo arms received a placebo for the duration of oseltamivir dosing after XOFLUZA or placebo dosing in that arm.
Adolescent subjects 12 to less than 20 years of age received weight-based XOFLUZA or placebo as a single oral dose. Seventy-eight percent of subjects in Trial T0831 were Asian, 17% were White, and 4% were Black or African American. In Trial T0831, 1,062 of 1,436 enrolled subjects had influenza confirmed by RT-PCR and were included in the efficacy analysis (XOFLUZA N=455, placebo N=230, or oseltamivir N=377).
Among subjects who received XOFLUZA and had influenza virus typed, influenza A/H3N2 was the predominant strain (90%), followed by influenza B (9%), and influenza A/H1N1 (2%). In both Trials T0821 and T0831, eligible subjects had an axillary temperature of at least 38˚C, at least one moderate or severe respiratory symptom (cough, nasal congestion, or sore throat), and at least one moderate or severe systemic symptom (headache, feverishness or chills, muscle or joint pain, or fatigue), and all were treated within 48 hours of symptom onset. Subjects participating in the trial were required to self-assess their influenza symptoms as "none," "mild," "moderate," or "severe" twice daily.
The primary efficacy population was defined as those with a positive rapid influenza diagnostic test (Trial T0821) or positive influenza reverse transcription polymerase chain reaction (RT-PCR) (Trial T0831) at trial entry. The primary endpoint of both trials, time to alleviation of symptoms, was defined as the time when all seven symptoms (cough, sore throat, nasal congestion, headache, feverishness, myalgia, and fatigue) had been assessed by the subject as none or mild for a duration of at least 21.5 hours. In both trials, XOFLUZA treatment at the recommended dose resulted in a statistically significant shorter time to alleviation of symptoms compared with placebo in the primary efficacy population ( Tables 10 and 11 ).
Table 10 Time to Alleviation of Symptoms After Single Dose in Otherwise Healthy Adults with Acute Uncomplicated Influenza in Trial T0821 (Median Hours) XOFLUZA 40 mg (95% CI CI: Confidence interval ) N=100 Placebo (95% CI ) N=100 Adults (20 to 64 Years of Age) 50 hours XOFLUZA treatment resulted in a statistically significant shorter time to alleviation of symptoms compared to placebo using the Gehan-Breslow's generalized Wilcoxon test (p-value: 0.014, adjusted for multiplicity using the Bonferroni method). The primary analysis using the Cox Proportional Hazards Model did not reach statistical significance (p-value: 0.165). 78 hours Table 11 Time to Alleviation of Symptoms After Single Dose in Otherwise Healthy Subjects 12 Years of Age and Older with Acute Uncomplicated Influenza in Trial T0831 (Median Hours) XOFLUZA 40 mg or 80 mg (95% CI CI: Confidence interval ) N=455 Placebo (95% CI ) N=230 Subjects (≥ 12 Years of Age) 54 hours XOFLUZA treatment resulted in a statistically significant shorter time to alleviation of symptoms compared to placebo using the Peto-Prentice's generalized Wilcoxon test (p-value: < 0.001). 80 hours In Trial T0831, there was no difference in the time to alleviation of symptoms between subjects (age ≥ 20 years) who received XOFLUZA (54 hours) and those who received oseltamivir (54 hours). The number of subjects who received XOFLUZA at the recommended dose and who were infected with influenza type B virus was limited, including 24 subjects in Trial T0821 and 38 subjects in Trial T0831.
In the influenza B subset in Trial T0831, the median time to alleviation of symptoms in subjects who received 40 mg or 80 mg XOFLUZA was 93 hours (95% CI of 53, 135) compared to 77 hours (95% CI of 47, 189) in subjects who received placebo.
Treatment of Acute Uncomplicated Influenza—High Risk Subjects (12 Years of Age and Older) Trial T0832 (NCT02949011) was a randomized, double-blind, placebo- and active-controlled trial to evaluate the efficacy and safety of a single oral dose of XOFLUZA compared with placebo or oseltamivir in adult and adolescent subjects 12 years of age or older with influenza who were at high risk of developing influenza-related complications. Twenty-eight percent of subjects were Asian, 59% were White, and 10% were Black or African American. High risk factors were based on the Centers for Disease Control and Prevention definition 1 of health factors known to increase the risk of developing serious complications from influenza.
The majority of subjects had underlying asthma or chronic lung disease, diabetes, heart disease, morbid obesity, or were 65 years of age or older. In Trial T0832, 1,158 of the 2,182 enrolled subjects had influenza confirmed by RT-PCR and were included in the efficacy analysis (XOFLUZA N=385, placebo N=385, or oseltamivir N=388). Among subjects in whom only one type/subtype of influenza virus was identified, 50% were infected with subtype A/H3N2, 43% were infected with type B, and 7% were infected with subtype A/H1N1.
A total of 215 subjects (19%) had preexisting symptoms (cough, muscle or joint pain, or fatigue) associated with their underlying high-risk condition that were worsened due to influenza infection. The primary efficacy endpoint was time to improvement of influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue). This endpoint included alleviation of new symptoms and improvement of any preexisting symptoms that had worsened due to influenza.
A statistically significant improvement in the primary endpoint was observed for XOFLUZA when compared with placebo (see Table 12 ). Table 12 Time to Improvement of Symptoms After Single Dose in High-Risk Subjects 12 Years of Age and Older with Acute Uncomplicated Influenza in Trial T0832 (Median Hours) XOFLUZA 40 mg or 80 mg The dosage of XOFLUZA was based on subject's weight. (95% CI CI: Confidence interval ) N=385 Placebo (95% CI ) N=385 73 hours XOFLUZA treatment resulted in a significant reduction in Time to Improvement of Influenza Symptoms compared to placebo using Peto-Prentice's generalized Wilcoxon test (p-value: < 0.001). 102 hours There was no statistically significant difference in the median time to improvement of influenza symptoms in the subjects who received XOFLUZA (73 hours) and those who received oseltamivir (81 hours). The median time to improvement of influenza symptoms in the limited number of adolescent subjects aged 12 to 17 years infected with influenza virus was similar for subjects who received XOFLUZA (188 hours) or placebo (191 hours) (N=13 and N=12, respectively).
Eligible subjects had a tympanic temperature of at least 38°C and at least one respiratory symptom of either cough or nasal congestion. Subjects at high risk of developing complications associated with influenza were included in the trial. The primary objective was to compare the safety of a single one-time dose of XOFLUZA with 5 days of oseltamivir administered twice daily.
The secondary efficacy endpoint included time to alleviation of influenza signs and symptoms, which was defined as the time when all of the following were met for at least 21.5 hours: cough and nasal symptoms were assessed by the caregiver as no problem or minor problem, subject was able to return to normal daily activity, and subject was afebrile (temperature ≤ 37.2°C). However, the trial was not powered to detect statistically significant differences in this secondary endpoint. The mean age was 8 years; 56% of subjects were female and 44% male.
The predominant influenza virus strain in this trial was the A/H3N2 subtype (67%), followed by A/H1N1 (20%) and type B (9%). Influenza-infected index patients were required to have onset of symptoms for ≤ 48 hours, and subjects (household contacts) were required to have lived with the influenza-infected index patient for ≥ 48 hours. A total of 715 subjects (XOFLUZA N=360, placebo N=355) 5 years of age and older were randomized and received a single oral dose of XOFLUZA according to body weight and age, or placebo, on Day 1.
The primary efficacy endpoint was the proportion of household subjects who were infected with influenza virus and presented with fever and at least one respiratory symptom from day 1 to day 10. Influenza infection was confirmed by RT-PCR, fever was defined as a body temperature (axillary) ≥ 37.5°C, and respiratory symptoms were defined as having a symptom of "cough" or "nasal discharge/nasal congestion" with a severity of moderate or severe as assessed by the subject. All subjects were Asian, 80% were female, and 20% were male.
In subjects that were 5 years of age and older, there was a statistically significant reduction in the proportion of household contacts (subjects) with laboratory-confirmed clinical influenza from 13% in the placebo group to 2% in the XOFLUZA group (see Table 13 ). In this age group, the proportion of subjects with laboratory-confirmed clinical influenza was 4% in the XOFLUZA group and 14% in the placebo group.
| XOFLUZA 40 mg (95% CI CI: Confidence interval ) N=100 | Placebo (95% CI ) N=100 | |
|---|---|---|
| Adults (20 to 64 Years of Age) | 50 hours XOFLUZA treatment resulted in a statistically significant shorter time to alleviation of symptoms compared to placebo using the Gehan-Breslow's generalized Wilcoxon test (p-value: 0.014, adjusted for multiplicity using the Bonferroni method). The primary analysis using the Cox Proportional Hazards Model did not reach statistical significance (p-value: 0.165). (45, 64) | 78 hours (68, 89) |
| XOFLUZA 40 mg or 80 mg (95% CI CI: Confidence interval ) N=455 | Placebo (95% CI ) N=230 | |
|---|---|---|
| Subjects (≥ 12 Years of Age) | 54 hours XOFLUZA treatment resulted in a statistically significant shorter time to alleviation of symptoms compared to placebo using the Peto-Prentice's generalized Wilcoxon test (p-value: < 0.001). (50, 59) | 80 hours (73, 87) |
| XOFLUZA 40 mg or 80 mg The dosage of XOFLUZA was based on subject's weight. (95% CI CI: Confidence interval ) N=385 | Placebo (95% CI ) N=385 |
|---|---|
| 73 hours XOFLUZA treatment resulted in a significant reduction in Time to Improvement of Influenza Symptoms compared to placebo using Peto-Prentice's generalized Wilcoxon test (p-value: < 0.001). (67, 85) | 102 hours (93, 113) |
| XOFLUZA (95% CI CI: Confidence interval (%) XOFLUZA treatment resulted in a significant reduction in the risk ratio of patients who were infected with influenza virus and presented with fever compared to placebo using modified Poisson regression for a binary response (p-value: < 0.0001). ) N=360 | Placebo (95% CI ) N=355 |
|---|---|
| 6 (2%) | 47 (13%) |
| (1%, 4%) | (10%, 17%) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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