About INBRIJA™

Efficacy and Safety Results

Pivotal Trial: SPANSM‑PD

The SPAN-PD trial demonstrated the efficacy of INBRIJA for treatment of OFF periods in patients with PD treated with oral CD/LD.

10 minutes

Onset of Action:

as early as 10 minutes postdose*

*Earliest timepoint assessed in study

30 minutes

Primary endpoint:

significant improvement in motor function at 30 minutes postdose (P=0.009)

60 minutes

Continuation of effect:

at 60 minutes postdose

Trial Design
Efficacy Results
Safety Results

SPAN-PD: STUDY DESIGN

The 12-week, randomized, double-blind, placebo-controlled SPAN-PD study evaluated the efficacy and safety of INBRIJA for treatment of OFF periods in patients with Parkinson's treated with CD/LD.

  • SPAN-PD was a multinational trial (US, Canada, Poland, and Spain)19
  • A total of 114 patients were treated with INBRIJA 84 mg, and 112 patients received placebo
  • Primary endpoint: Change in Unified Parkinson's Disease Rating Scale (UPDRS)* Part III motor score from predose OFF to 30 minutes postdose with INBRIJA 84 mg vs placebo at Week 12

*UPDRS Part III is a composite score of 14 items designed to assess the severity of primary motor symptoms in patients with PD.20

IN-CLINIC DOSING AT WEEKS 0, 4, 8, AND 121,19
  • Patients took morning CD/LD as usual and arrived in the ON state
  • Patients remained in clinic until they transitioned into an OFF period
  • Patients self-administered study drug at the start of the OFF period
USE AT HOME1,19
  • Used at the start of an OFF period
  • Continued use of usual PD medications including CD/LD
  • Self-administered as needed up to a maximum of 5 times during the waking day
  • Use of INBRIJA for early‑morning OFF was excluded
Usual-care aspects of study design

The SPAN‑PD trial reflected the way patients would use INBRIJA on‑demand for OFF periods in addition to their CD/LD-based Parkinson's therapy:

  • Patients used INBRIJA at the onset of an OFF period, as needed (once per OFF period up to a maximum of 5 times a day) during the waking day
  • Patients continued taking their usual Parkinson's medications including CD/LD
Selected Important Safety Information
  • INBRIJA is not recommended in patients with asthma, COPD, or other chronic underlying lung disease because of the risk of bronchospasm.
  • Use of selective MAO-B inhibitors with INBRIJA may be associated with orthostatic hypotension. Monitor patients taking these drugs concurrently.

Please see additional Important Safety Information below.

PATIENTS AT BASELINE HAD: KEY EXCLUSION CRITERIA
  • CD/LD regimen not exceeding 1600 mg/day of levodopa
  • ≥2 hours of OFF time per day
  • Modified Hoehn and Yahr Stage 1 to 3 (mild to moderate), as measured in ON state19
  • Mean UPDRS Part III motor scores in ON state at screening: 14.9 for INBRIJA 84 mg and 16.1 for placebo
  • Patients with asthma, COPD, or other chronic respiratory disease within the last 5 years1
  • Use of apomorphine19

BASELINE PATIENT CHARACTERISTICS1,19 (N=226)

CHARACTERISTICS MEAN VALUE
Age (range, 38-82 yr) 63.0 yr
Gender (male)* 75%
Ethnicity (white)* 95%
Time since diagnosis 8.0 yr
Number of OFF periods/day 3.4
Duration of oral levodopa treatment 6.5 yr
Daily oral levodopa dose 830 mg
Number of daily oral levodopa doses 5.1
Hoehn and Yahr stage <2.5* 64.6%

*Not mean value
Including early morning

Selected Important Safety Information
  • Patients treated with levodopa, the active ingredient in INBRIJA, have reported falling asleep during activities of daily living, including operation of motor vehicles, which sometimes resulted in accidents. Many patients reported somnolence but some reported no warning signs (sleep attack). This may occur more than a year after initiating treatment. Reassess patients for drowsiness/sleepiness including occurrence during specific activities. Advise patients of potential for drowsiness and ask about factors that may increase this risk (e.g., sedating medications, sleep disorders).
    • Consider discontinuing INBRIJA in patients who report significant daytime sleepiness or falling asleep during activities that require active participation. If continuing INBRIJA, advise patients not to drive and to avoid activities that may result in harm. There is insufficient information that dose reduction will eliminate episodes of falling asleep during activities of daily living.

Please see additional Important Safety Information below.

SPAN-PD: INBRIJA SIGNIFICANTLY IMPROVED MOTOR FUNCTION IN PATIENTS WITH PARKINSON’S EXPERIENCING OFF PERIODS ON CD/LD

UPDRS Part III motor score change from 0‑60 minutes postdose at week 12

SE, standard error.

Responder ON

A significantly greater proportion of patients taking INBRIJA 84 mg (58%) vs placebo (36%) returned to an ON state and sustained that ON through 60 minutes postdose (P=0.003).

Selected Important Safety Information
  • Neuroleptic malignant syndrome‑like symptoms (e.g., elevated temperature, muscular rigidity, altered consciousness, autonomic instability) have been reported with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy.
  • Hallucinations (with or without confusion, insomnia, and excessive dreaming) may occur and may respond to reducing levodopa therapy. Abnormal thinking and behavior may present with paranoid ideation, delusions, hallucinations, confusion, psychotic‑like behavior, disorientation, aggressive behavior, agitation, and delirium.
  • INBRIJA should ordinarily not be used in patients with major psychotic disorder due to risk of exacerbating psychosis. Dopamine antagonists used to treat psychosis may exacerbate symptoms of PD and may decrease INBRIJA efficacy.

Please see additional Important Safety Information below.

SPAN-PD: SAFETY RESULTS

The 12-week, randomized, double-blind, placebo-controlled SPAN-PD study evaluated the efficacy and safety of INBRIJA for treatment of OFF periods in patients with Parkinson's treated with CD/LD.

ADVERSE REACTIONS OCCURRING IN ≥5% OF INBRIJA‑TREATED PATIENTS AND MORE FREQUENTLY THAN PLACEBO

ADVERSE REACTION INBRIJA 84 mg (n=114) PLACEBO (n=112)
Cough 15% 2%
Upper respiratory tract infection 6% 3%
Nausea 5% 3%
Sputum discolored 5% 0%

Inhalation of INBRIJA can lead to coughing at the time of administration.

Additional respiratory‑related adverse reactions ≥2% and at a higher rate than placebo: nasopharyngitis (3% vs 2%), and nasal discharge discoloration, oropharyngeal pain, bronchitis/pneumonia (each 2% vs 0%).



DISCONTINUATIONS DUE TO ADVERSE REACTIONS
INBRIJA 84 mg: 6 patients (5%)
Placebo: 3 patients (3%)
The most common adverse reaction leading to discontinuation of INBRIJA 84 mg was cough (2 patients vs none for placebo).
Selected Important Safety Information
  • Patients on medications that increase central dopaminergic tone such as INBRIJA can experience intense urges to gamble or spend money, increased sexual urges, binge eating, and/or other intense urges, and inability to control them. In some cases, these urges stopped with dose reduction or medication discontinuation. Since some patients may not recognize these behaviors as abnormal, ask patients or their caregivers about development of new or increased urges and consider stopping INBRIJA if this occurs.
  • INBRIJA may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, consider stopping INBRIJA or adjusting other PD medications.
  • INBRIJA is not recommended in patients with asthma, COPD, or other chronic underlying lung disease because of the risk of bronchospasm.
  • Geriatric patients (n=56) experienced more of the following adverse reactions than patients <65 (n=58): cough (25% vs 5%), upper respiratory tract infection (11% vs 2%), nausea (7% vs 3%), vomiting (4% vs 2%), pain in extremities (4% vs 0%), and discolored nasal discharge (4% vs 0%).

Please see additional Important Safety Information below.

INBRIJA™ Indication

Intermittent treatment of OFF episodes in patients with PD treated with CD/LD.

Important Safety Information

  • Contraindication: nonselective MAOIs (e.g., phenelzine, tranylcypromine) due to hypertension risk. Discontinue their use at least 2 weeks prior to initiating INBRIJA.
  • Not recommended in patients with asthma/COPD/other chronic lung disease due to bronchospasm risk.
See more

Indication

INBRIJA is indicated for intermittent treatment of OFF episodes in patients with Parkinson’s disease (PD) treated with carbidopa/levodopa.

Important Safety Information

  • INBRIJA is contraindicated in patients taking or who have recently taken (within 2 weeks) nonselective monoamine oxidase (MAO) inhibitors (e.g., phenelzine and tranylcypromine) due to risk of hypertension. Discontinue use of nonselective MAO inhibitors at least 2 weeks prior to initiating INBRIJA.
  • Patients treated with levodopa, the active ingredient in INBRIJA, have reported falling asleep during activities of daily living, including operation of motor vehicles, which sometimes resulted in accidents. Many patients reported somnolence but some reported no warning signs (sleep attack). This may occur more than a year after initiating treatment. Reassess patients for drowsiness/sleepiness including occurrence during specific activities. Advise patients of potential for drowsiness and ask about factors that may increase this risk (e.g., sedating medications, sleep disorders).
    • Consider discontinuing INBRIJA in patients who report significant daytime sleepiness or falling asleep during activities that require active participation. If continuing INBRIJA, advise patients not to drive and to avoid activities that may result in harm. There is insufficient information that dose reduction will eliminate episodes of falling asleep during activities of daily living.
  • Neuroleptic malignant syndrome-like symptoms (e.g., elevated temperature, muscular rigidity, altered consciousness, autonomic instability) have been reported with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy.
  • Hallucinations (with or without confusion, insomnia, and excessive dreaming) may occur and may respond to reducing levodopa therapy. Abnormal thinking and behavior may present with paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.
  • INBRIJA should ordinarily not be used in patients with major psychotic disorder due to risk of exacerbating psychosis. Dopamine antagonists used to treat psychosis may exacerbate symptoms of PD and may decrease INBRIJA efficacy.
  • Patients on medications that increase central dopaminergic tone such as INBRIJA can experience intense urges to gamble or spend money, increased sexual urges, binge eating, and/or other intense urges, and inability to control them. In some cases, these urges stopped with dose reduction or medication discontinuation. Since some patients may not recognize these behaviors as abnormal, ask patients or their caregivers about development of new or increased urges and consider stopping INBRIJA if this occurs.
  • INBRIJA may cause or exacerbate dyskinesias. If troublesome dyskinesias occur, consider stopping INBRIJA or adjusting other PD medications.
  • INBRIJA is not recommended in patients with asthma, COPD, or other chronic underlying lung disease because of the risk of bronchospasm.
  • Monitor patients with glaucoma for increased intraocular pressure.
  • Abnormalities in laboratory tests may include elevations of liver function tests (e.g., alkaline phosphatase, AST, ALT, lactic dehydrogenase, bilirubin), blood urea nitrogen, hemolytic anemia, and positive direct antibody test. Increased levels of catecholamines and their metabolites in plasma and urine may result in false-positive results suggesting pheochromocytoma.
  • The most common adverse reactions (≥ 5% and > placebo) were cough (15% vs 2%), upper respiratory tract infection (6% vs 3%), nausea (5% vs 3%), and sputum discolored (5% vs 0%).
  • Use of selective MAO-B inhibitors with INBRIJA may be associated with orthostatic hypotension. Monitor patients taking these drugs concurrently.
  • Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide) and isoniazid may reduce levodopa efficacy; monitor for worsening symptoms.
  • Iron salts or multivitamins with iron salts may reduce levodopa bioavailability.
  • INBRIJA should be used during pregnancy/nursing only if potential benefit justifies potential risk. There are no adequate data on INBRIJA in pregnant women or breastfed infants. Animal data shows carbidopa/levodopa is developmentally toxic (including teratogenicity). Levodopa may affect milk production, interfering with lactation. Levodopa has been detected in human milk.
  • Safety and effectiveness in pediatric patients have not been established.
  • Geriatric patients (n=56) experienced more of the following adverse reactions than patients <65 (n=58): cough (25% vs 5%), upper respiratory tract infection (11% vs 2%), nausea (7% vs 3%), vomiting (4% vs 2%), pain in extremities (4% vs 0%), and discolored nasal discharge (4% vs 0%).

Please see the Full Prescribing Information.