Ensifentrine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh
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Overview
Ensifentrine is a {{{drugClass}}} that is FDA approved for the treatment of OHTUVAYRE is a phosphodiesterase 3 (PDE3) inhibitor and phosphodiesterase 4 (PDE4) inhibitor approved for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.. Common adverse reactions include {{{adverseReactions}}}.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
OHTUVAYRE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.
The recommended dosage of OHTUVAYRE is 3 mg (one unit-dose ampule) twice daily, once in the morning and once in the evening, administered by oral inhalation using a standard jet nebulizer with a mouthpiece.
Administration Instructions:
• Remove OHTUVAYRE unit-dose ampule from foil pouch only immediately before use.
• Shake OHTUVAYRE ampule vigorously.
• Squeeze and completely empty contents of the ampule into the nebulizer cup for
administration of OHTUVAYRE by oral inhalation. Discard ampule with any residual
content.
• Administer OHTUVAYRE by oral inhalation using a standard jet nebulizer equipped with
a mouthpiece, connected to an air compressor.
Drug Compatibility:
• Compatibility of OHTUVAYRE mixed with other drugs has not been established. OHTUVAYRE
should not be physically mixed with other drugs or added to solutions containing
other drugs.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ensifentrine in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ensifentrine in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
The safety and effectiveness of OHTUVAYRE have not been established in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ensifentrine in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ensifentrine in pediatric patients.
Contraindications
OHTUVAYRE is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.
Warnings
• Acute Episodes of Bronchospasm
OHTUVAYRE should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. OHTUVAYRE has not been studied in the relief of acute symptoms and extra doses of OHTUVAYRE should not be used for that purpose. The safety and effectiveness of OHTUVAYRE for relief of acute symptoms have not been established. Acute symptoms should be treated with an inhaled, short-acting bronchodilator. • Paradoxical Bronchospasm
As with other inhaled medicines, OHTUVAYRE may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with OHTUVAYRE, it should be treated immediately with an inhaled, short-acting bronchodilator. OHTUVAYRE should be discontinued immediately and alternative therapy should be instituted. • Psychiatric Events Including Suicidality
Treatment with OHTUVAYRE is associated with an increase in psychiatric adverse reactions. Psychiatric events including suicide-related adverse reactions were reported in clinical studies in patients who received OHTUVAYRE. One patient who received OHTUVAYRE in the pooled 24-week safety population. experienced a suicide-related adverse reaction (suicide attempt), and in another controlled study, one patient who received ensifentrine experienced a suicide-related adverse reaction (suicide). Additionally, the most commonly reported psychiatric adverse reactions in the pooled 24-week safety population were insomnia (6 patients [0.6%] OHTUVAYRE 3 mg; 2 patients [0.3%] placebo), and anxiety (2 patients [0.2%] OHTUVAYRE 3 mg; 1 patient [0.2%] placebo). Depression-related reactions including depression, major depression, and adjustment disorder with depressed mood occurred in 4 patients [0.4%] receiving OHTUVAYRE and no patients receiving placebo. Before initiating treatment with OHTUVAYRE, healthcare providers should carefully weigh the risk and benefits of treatment with OHTUVAYRE in patients with a history of depression and/or suicidal thoughts or behavior. Healthcare providers should carefully evaluate the risks and benefits of continuing treatment with OHTUVAYRE if such events occur.
Adverse Reactions
Clinical Trials Experience
• Paradoxical Bronchospasm.
• Psychiatric Events Including Suicidality.
• 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 safety of OHTUVAYRE was based on the pooled safety population from two randomized, double-blind, placebo-controlled trials (ENHANCE-1 and ENHANCE-2) for 24 weeks, and a 48-week cohort that assessed safety in ENHANCE-1. In these trials, a total of 975 patients received 3 mg of OHTUVAYRE twice daily administered by oral inhalation using a standard jet nebulizer .The safety population included all patients who were randomized and received at least one dose of OHTUVAYRE or placebo.
Adverse reactions that occurred at an incidence greater than or equal to 1% in OHTUVAYRE and were more common than placebo in the pooled population are provided in Table 1. The proportion of patients who discontinued treatment due to adverse reactions was 7.6% for the OHTUVAYRE-treated patients and 8.2% for placebo-treated patients. In the pooled 24-week safety population from the ENHANCE-1 and ENHANCE-2 trials, adverse reactions with an incidence of 1% or more and occurring more frequently in patients receiving OHTUVAYRE compared to placebo were reported. Among the 975 patients treated with OHTUVAYRE, back pain was observed in 18 patients (1.8%) versus 6 patients (1.0%) in the placebo group. Hypertension occurred in 17 patients (1.7%) receiving OHTUVAYRE, compared to 5 patients (0.9%) on placebo. Urinary tract infections were reported in 13 patients (1.3%) in the OHTUVAYRE group and in 6 patients (1.0%) receiving placebo. Diarrhea was experienced by 10 patients (1.0%) on OHTUVAYRE compared to 4 patients (0.7%) in the placebo group. These findings indicate that these specific adverse reactions were more frequently reported with OHTUVAYRE than with placebo in patients with COPD.
Adverse Reactions in the 48-Week Cohort:
In the 48-week cohort of ENHANCE-1, 369 patients were enrolled to be treated with 3 mg OHTUVAYRE (N=280) or placebo (N=89) twice daily for 48 weeks. The adverse reactions reported in the 48-week cohort were consistent with those observed in the pooled 24-week safety population.
Postmarketing Experience
There is limited information regarding Ensifentrine Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Ensifentrine Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): There are no available data on OHTUVAYRE use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, administration of inhaled ensifentrine at exposures 30 times the exposure at the maximum recommended human daily inhalation dose (MRHDID) to male rats for 10 weeks prior to mating with untreated females produced increased pre- and post- implantation loss, and decreased live embryos in untreated female rats. No adverse developmental effects were observed with inhalation administration of ensifentrine to pregnant rats and rabbits during organogenesis at maternal exposures up to 79 and 9 times the exposure at MRHDID, respectively. No adverse developmental effects were observed after inhaled administration of ensifentrine to pregnant rats from the period of organogenesis through lactation at exposures up to approximately 79 times the MRHDID. (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 defect, 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% to 4% and 15% to 20%, respectively.
Data:
Animal Data
In a male fertility study, ensifentrine was administered to male rats at inhalation doses of 2, 6, and 16 mg/kg/day (4, 13, and 30 times the exposure at the MRHDID) for 10 weeks prior to mating to untreated females. Adverse effects at 16 mg/kg/day (30 times the exposure at the MRHDID) on reproductive performance included increased pre- and post- implantation loss, and decreased live embryos per litter in untreated females. No developmental toxicity was observed in rats at 6 mg/kg/day (13 times the exposure at the MRHDID).
In an embryo-fetal development study, pregnant rats were administered ensifentrine at inhalation doses of up to 15 mg/kg/day (79 times the exposure at the MRHDID) during the period of organogenesis from gestation Days 6 to 17. Ensifentrine did not cause adverse effects to the fetus at exposures up to 79 times the MRHDID (on an AUC basis at a maternal inhalation dose of 15 mg/kg/day).
In an embryo-fetal development study, pregnant rabbits were administered ensifentrine at inhalation doses of up to 12 mg/kg/day (9 times the exposure at the MRHDID) during the period of organogenesis from gestation Days 6 to 19. Ensifentrine did not cause adverse effects to the fetus at maternal exposures up to 9 times the MRHDID.
In a pre- and post-natal development (PPND) study, pregnant rats were administered ensifentrine at inhalation doses of up to 19 mg/kg/day (approximately 79 times the exposure at the MRHDID) from gestation day 6 to lactation/post-partum day 24. No adverse effects were observed in the offspring exposed daily from birth (in utero) through lactation at maternal pulmonary deposited doses up to approximately 79 times the MRHDID.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ensifentrine in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Ensifentrine during labor and delivery.
Nursing Mothers
There are no data on the presence of ensifentrine in human milk, the effects on the breastfed child, or the effects on milk production. There are no data from animal studies on the presence of ensifentrine in milk.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for OHTUVAYRE and any potential adverse effects on the breastfed child from OHTUVAYRE or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of OHTUVAYRE have not been established in pediatric patients.
Geriatic Use
There were 852 patients aged 65 years and older in ENHANCE-1 and ENHANCE-2 for COPD.
Of the total number of patients randomized to receive OHTUVAYRE in these trials, 534 (55%) were 65 years of age and older, while 84 (9%) were 75 years and older. No overall differences in safety or effectiveness of OHTUVAYRE have been observed between these patients and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.
Gender
There is no FDA guidance on the use of Ensifentrine with respect to specific gender populations.
Race
There is no FDA guidance on the use of Ensifentrine with respect to specific racial populations.
Renal Impairment
No dosage adjustment in patients with mild or moderate renal impairment is required. Patients with severe renal impairment have not been evaluated.
Hepatic Impairment
Ensifentrine systemic exposure increased by 2.3-fold in subjects with moderate or severe hepatic impairment compared with healthy subjects.
Use OHTUVAYRE with caution in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Ensifentrine in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Ensifentrine in patients who are immunocompromised.
Administration and Monitoring
Administration
Administration Instructions:
Remove OHTUVAYRE unit-dose ampule from foil pouch only immediately before use.
Shake OHTUVAYRE ampule vigorously.
Squeeze and completely empty contents of the ampule into the nebulizer cup for administration of OHTUVAYRE by oral inhalation. Discard ampule with any residual content.
Administer OHTUVAYRE by oral inhalation using a standard jet nebulizer equipped with a mouthpiece, connected to an air compressor.
Monitoring
Drug Compatibility:
Compatibility of OHTUVAYRE mixed with other drugs has not been established. OHTUVAYRE should not be physically mixed with other drugs or added to solutions containing other drugs.
IV Compatibility
There is limited information regarding the compatibility of Ensifentrine and IV administrations.
Overdosage
An overdosage of OHTUVAYRE may lead to signs and symptoms such as headache, tachycardia, and palpitations. Treatment of overdosage consists of temporary interruption of OHTUVAYRE along with appropriate symptomatic and/or supportive therapy.
Pharmacology
There is limited information regarding Ensifentrine Pharmacology in the drug label.
Mechanism of Action
Ensifentrine is a small molecule that is an inhibitor of the PDE3 and PDE4 enzymes. PDE3 primarily hydrolyzes the second-messenger molecule cyclic adenosine monophosphate (cAMP) but is also capable of hydrolyzing cyclic guanosine monophosphate (cGMP). PDE4 hydrolyzes cAMP only. Inhibition of PDE3 and PDE4 results in accumulation of intracellular levels of cAMP and/or cGMP, resulting in various downstream signalling effects.
Structure
OHTUVAYRE (ensifentrine) is a sterile, yellow to pale yellow aqueous inhalation suspension of ensifentrine for oral inhalation. Ensifentrine, the active component of OHTUVAYRE, is an inhibitor of phosphodiesterases 3 and 4 ( PDE3 and PDE4 ) . The chemical name for ensifentrine is N- ( 2- { ( 2E ) -9,10-dimethoxy-4-oxo-2- [ ( 2,4,6-trimethylphenyl ) imino ] -6,7-dihydro-2H-pyrimido [ 6,1-a ] isoquinolin-3 ( 4H ) –yl }ethyl ) urea.
Pharmacodynamics
Cardiac Electrophysiology:
QTc interval prolongation was studied in a randomized, double-blind, placebo- and positive-controlled, 4-period crossover study in 32 healthy subjects. At 3 times the maximum recommended dose, clinically significant QTc interval prolongation was not observed.
Pharmacokinetics
Exposure to ensifentrine increased approximately 1.4-fold greater than dose proportional following a dose 3 times the recommended dosage. Steady-state was attained by Day 3 following twice-daily dosing. Population pharmacokinetic analysis predicts accumulation of ensifentrine of 1.3 and 1.4-fold for Cmax and AUC in healthy subjects and 1.4 and 1.5-fold for Cmax and AUC in subjects with COPD. Population pharmacokinetic analysis indicates that relative bioavailability in subjects with COPD is approximately 35% lower when compared to healthy subjects. Exposure to ensifentrine was associated with high inter-subject variability.
• Absorption:
Following inhaled administration of OHTUVAYRE in healthy subjects and subjects with COPD, ensifentrine Cmax was attained around 0.6 to 1.5 hours after dosing. A randomized, 2-period, cross-over study assessing systemic exposure following inhalation of 2 times the recommended dose of ensifentrine with and without charcoal block demonstrated that the majority of an inhaled dose (approximately 90%) is delivered to the lung from which it is absorbed.
• Distribution:
Apparent central and peripheral volume of distribution for ensifentrine in healthy subjects were 2700 L and 1820 L, respectively, as estimated in population PK analysis. In patients with COPD, apparent central and peripheral volumes were estimated as 8150 L and 5490 L, respectively. In vitro plasma protein binding of ensifentrine is approximately 90%.
• Elimination:
Following twice-daily administration for 6 days, terminal elimination half-life ranged from 10.6 to 12.6 hours in healthy subjects and subjects with COPD (1.5 mg to 12 mg twice daily).
• Metabolism:
Following administration of a single nebulized dose, 8 times the recommended dose of ensifentrine, unchanged ensifentrine was identified as the major drug-related component in human plasma, accounting for 96 and 99% of the drug-related material identified in Tmax and time-normalized (0-24 h) plasma samples, respectively. The primary metabolic routes for ensifentrine are oxidative (hydroxylation, O-demethylation) followed by conjugation (e.g., glucuronidation). In vitro results indicate that, at physiologically relevant concentrations, ensifentrine was predominantly metabolized by CYP2C9 and to a lesser extent by CYP2D6.
• Excretion:
The majority of ensifentrine is excreted in feces. After a 3 mg nebulized dose, urinary elimination of unchanged ensifentrine was negligible (<0.3% of the dose).
Specific Populations
Population pharmacokinetic analysis showed no evidence of a clinically significant effect of demographic covariates such as age (18 to 80 years), sex (56% male), ethnicity (Hispanic, Non-Hispanic), race (white, black) and weight (42 to 180 kg) on ensifentrine pharmacokinetics.
• Patients with Renal Impairment:
A dedicated study with OHTUVAYRE evaluating the effect of renal impairment on the pharmacokinetics of ensifentrine was not conducted. The effect of renal impairment on the exposure to ensifentrine for up to 24 weeks was evaluated in a population pharmacokinetic analysis. Estimated glomerular filtration rate (eGFR) varied from 25.5 to 191 mL/min representing a range of moderate to no renal impairment. While continuous covariates of renal function did not show a significant correlation with ensifentrine exposure, categorical characterization of renal function indicated a 25% mean reduction in the apparent clearance in subjects with moderate renal impairment. The pharmacokinetics of ensifentrine in severe renal impairment (creatine clearance <30 mL/min) or subjects with end-stage renal disease have not been evaluated.
• Patients with Hepatic Impairment:
The pharmacokinetics of ensifentrine were evaluated in subjects with moderate (Child-Pugh Class B) (N=10) to severe (Child-Pugh Class C) (N=2) hepatic impairment. Ensifentrine Cmax and AUCinf were approximately 2.3-fold and 2.2-fold higher in subjects with moderate hepatic impairment compared with healthy controls. Ensifentrine Cmax and AUCinf were approximately 1.2-fold and 2.3-fold higher in subjects with severe hepatic impairment compared with healthy controls (N=7).
Population PK analysis did not identify markers of liver function (ALT, AST, bilirubin, and ALP) as a significant covariate for exposure of ensifentrine.
• Drug Interaction Studies:
Effect of Other Drugs on OHTUVAYRE
• Clinical Studies:
Ensifentrine and Cytochrome P450: Ensifentrine Cmax and AUC0-inf were 1.4-fold and 1.6-fold higher; respectively, when a 3 mg single dose of OHTUVAYRE was concomitantly administered with CYP2C9 inhibitor fluconazole (200 mg twice daily). In Vitro Studies Ensifentrine and Efflux Transporters: Ensifentrine is not a substrate of the efflux transporter P-glycoprotein (P-gp). Ensifentrine is a substrate of breast cancer resistance protein (BCRP). Ensifentrine and Uptake Transporters: Ensifentrine is not a substrate of the uptake transporters OATP1B1 or OATP1B3. Effect of OHTUVAYRE on Other Drugs
• In Vitro Studies:
Ensifentrine and Cytochrome P450: At therapeutically relevant concentrations, ensifentrine does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. Ensifentrine and Efflux Transporters: At therapeutically relevant concentrations, ensifentrine is not an inhibitor of either BCRP or P-gp. Ensifentrine and Uptake Transporters: Ensifentrine does not inhibit the transporters, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 or MATE2-K, at therapeutically relevant concentrations.
Nonclinical Toxicology
A two-year inhalation study in Han Wistar rats and a 6-month oral study in Tg.rasH2 transgenic mice were conducted to assess the carcinogenic potential of ensifentrine. No evidence of tumorigenicity was observed in male and female rats at an exposure approximately 40 times the MRHDID. No evidence of tumorigenicity was observed in male and female Tg.rasH2 mice at oral doses up to 80 mg/kg/day, the highest dose tested.
Ensifentrine was negative for genotoxicity in the following assays: in vitro Ames test for bacterial gene mutation, in vivo comet test with rats, or in vivo micronucleus assay with mice.
In a male fertility study, ensifentrine was administrated to male rats at inhalation doses of 2, 6, and 16 mg/kg/day (4, 13, and 30 times the exposure at the MRHDID) for 10 weeks prior to mating to untreated females. Male rats had decreased sperm motility and increased abnormal sperm morphology at an inhalation dose of 16 mg/kg/day (approximately 30 times the exposure at the MRHDID). Decreased sperm counts in the testis were observed at all doses. Atrophy/degeneration in the testis and intraluminal germ cell debris in the epididymis were observed at doses of 6 (13 times the exposure at the MRHDID) and 16 mg/kg/day (30 times the exposure at the MRHDID). Additional adverse effects at 16 mg/kg/day on reproductive performance included decreased mating index and decreased fertility index. The sperm counts, sperm motility, and sperm morphology were reversible at the end of a 4-week treatment-free period. Atrophy/degeneration in the testis and intraluminal germ cell debris in the epididymis were not present at the end of a 4-week treatment-free period. In a female fertility study, ensifentrine was administrated to female rats at inhalation doses of up to 18 mg/kg/day from two weeks prior to mating to 7 days after mating. Ensifentrine had no effect on female fertility and reproductive performance indices up to 18 mg/kg/day (31 times the exposure at the MRHDID).
Clinical Studies
The efficacy of OHTUVAYRE was evaluated in two 24-week randomized, double-blind, placebo-controlled, parallel-group clinical trials (ENHANCE-1 [NCT04535986] and ENHANCE-2 [NCT04542057]). The two trials enrolled a total of 1553 adults with moderate to severe COPD.
ENHANCE-1 enrolled a total of 763 patients randomized 5:3 to receive 3 mg of OHTUVAYRE administered by oral inhalation via standard jet nebulizer such as PARI LC Sprint, or placebo. Patients in ENHANCE-1 had a mean age of 65 years (range: 41 to 80 years), were 58% male, 90% White, 3% Black/African American, 3% Asian, 0.1% Other race, and 3% Hispanic or Latino ethnicity. Patients had a mean smoking history of 41 pack-years and 57% were current smokers, and 25% of patients reported exacerbations of COPD within the 15 months prior to the study. At screening, the mean post-bronchodilator percent predicted FEV1 was 52% (range: 27% to 85%), and the mean post-bronchodilator FEV1/FVC ratio was 0.52 (range: 0.22 to 0.71). In addition, 68% of patients were taking concurrent therapy: 30% taking concurrent LAMA, 18% taking concurrent LABA, and 20% taking concurrent LABA/ICS therapy throughout the trial.
ENHANCE-2 enrolled a total of 790 patients randomized 5:3 to receive 3 mg of OHTUVAYRE twice daily administered by oral inhalation via a standard jet nebulizer such as PARI LC Sprint or placebo. Patients in ENHANCE-2 had a mean age of 65 years (range: 40 to 80 years), were 52% female, 95% White, 4% Black/African American, 0.3% Asian, 0.5% Other race, and 5% Hispanic or Latino ethnicity. Patients had a mean smoking history of 42 pack-years and 55% were current smokers, and 21% of patients reported exacerbations of COPD within the 15 months prior to the study.
At screening, the mean post-bronchodilator percent predicted FEV1 was 51% (range: 23% to 81%), and the mean post-bronchodilator FEV1/FVC ratio was 0.52 (range: 0.24 to 0.71). In addition, 55% of patients were taking concurrent therapy: 33% taking concurrent LAMA, 7% taking concurrent LABA, and 15% taking concurrent LABA/ICS therapy throughout the trial.
The primary endpoint for ENHANCE-1 and ENHANCE-2 was the change from baseline in FEV1 AUC0-12h post dose at Week 12. In both trials, OHTUVAYRE demonstrated a statistically significant improvement in FEV1 AUC0-12h compared to placebo. Refer to Table 2 for the primary endpoint results. In the ENHANCE-1 and ENHANCE-2 clinical trials, the least squares (LS) mean change from baseline in FEV₁ AUC₀–₁₂h (mL) at Week 12 demonstrated greater improvement with OHTUVAYRE compared to placebo. In ENHANCE-1, among patients who received at least one dose of study drug and had a non-missing baseline FEV₁ value (n=477 for OHTUVAYRE and n=282 for placebo), the LS mean change was 61 mL (95% CI: 25, 97) for OHTUVAYRE and -26 mL (95% CI: -64, 13) for placebo, resulting in an LS mean difference from placebo of 87 mL (95% CI: 55, 118; p<0.0001). In ENHANCE-2, the LS mean change was 48 mL (95% CI: 30, 66) for OHTUVAYRE (n=498) and -46 mL (95% CI: -70, -22) for placebo (n=291), yielding an LS mean difference of 94 mL (95% CI: 65, 124; p<0.0001). These results indicate a statistically significant improvement in lung function with OHTUVAYRE treatment compared to placebo.
In ENHANCE-1 and ENHANCE-2, serial spirometry was performed over 12 hours in all patients at baseline and Week 12. Serial spirometry data for ENHANCE-1 at Week 12 are shown.
In the ENHANCE-1 trial, the mean FEV₁ (mL) change from baseline over 12 hours at Week 12 demonstrated an improvement in lung function with OHTUVAYRE treatment. Trough FEV₁, defined as the last FEV₁ value collected prior to the morning dose, showed a statistically significant improvement of 35 mL (95% CI: 14, 68) in ENHANCE-1 relative to placebo. In ENHANCE-2, the improvement in morning trough FEV₁ at Week 12 was 49 mL (95% CI: 19, 80); however, this result was not considered statistically significant due to a failure higher in the pre-specified testing hierarchy. These findings suggest a positive effect of OHTUVAYRE on pulmonary function, particularly as demonstrated in the ENHANCE-1 study.
• Health-Related Quality of Life:
The St. George's Respiratory Questionnaire (SGRQ) was assessed in ENHANCE-1 and ENHANCE-2. In ENHANCE-1, the SGRQ responder rate (defined as an improvement in score of 4 or more as threshold) for OHTUVAYRE at Week 24 was 58.2% compared to 45.9% for placebo [Odds Ratio: 1.49; 95% CI: 1.07, 2.07]. In ENHANCE-2, the SGRQ responder rate for OHTUVAYRE at Week 24 was 45.4% compared to 50.3% for placebo [Odds Ratio: 0.92; 95% CI: 0.66, 1.29].
How Supplied
OHTUVAYRE (ensifentrine) 3 mg/2.5 mL inhalation suspension is a sterile aqueous suspension in a unit-dose low-density polyethylene ampule. OHTUVAYRE is supplied in a carton of 60 unit-dose ampules (NDC 83034-003-60). Each ampule is overwrapped in a sealed foil pouch. The ampule containing OHTUVAYRE should be shaken vigorously to ensure complete resuspension of the active ingredient immediately prior to use. The used ampule and any residual content should be discarded after use.
Storage
Store OHTUVAYRE in the protective foil pouch (only remove from foil pouch immediately before use) at controlled room temperature (68°F to 77°F [20°C to 25°C], excursions permitted from 59ºF to 86ºF [15ºC to 30ºC]) [See USP Controlled Room Temperature], maintaining the orientation indicated on the carton. Protect from direct sunlight and excessive heat. Do not freeze.
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Patient Counseling Information
There is limited information regarding Ensifentrine Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Ensifentrine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Ensifentrine Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Ensifentrine Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.