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Armodafinil

Phase 3

Depression | Small molecule | Psychiatry |Teva Pharmaceutical Industries Limited|Last Updated: Nov 9, 2021

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment1,324

FDA Designations

No designations recorded

Clinical trial landscape

Armodafinil · 11 trials · 8 indications

Phase 3 7Phase 2 3Phase 1 1
NCT01305408Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 mg/Day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I DisorderDepression
COMPLETED399 Analytics
NCT01072630Study to Evaluate the Efficacy and Safety of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I DisorderDepression
COMPLETED492 Analytics
NCT01072929A Study to Evaluate the Efficacy and Safety of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I DisorderDepression
COMPLETED433 Analytics
NCT00758498Study of the Effect of Armodafinil Treatment in Healthy Subjects With Excessive Sleepiness Associated With Jet Lag DisorderExcessive Sleepiness
COMPLETED427 Analytics
NCT00228566Study to Assess Patient Reported Outcomes With Armodafinil Treatment for Excessive Sleepiness in Adults With Narcolepsy or Obstructive Sleep Apnea/Hypopnea SyndromeExcessive Daytime Sleepiness
COMPLETED247 Analytics
NCT00078377Safety and Efficacy Study of Armodafinil (CEP-10953) in the Treatment of Excessive Sleepiness Associated With NarcolepsyNarcolepsy
COMPLETED196 Analytics
NCT00080288Safety/Efficacy Study With Armodafinil (CEP-10953) in Treatment of Excessive Sleepiness Associated With Chronic SWSDExcessive Sleepiness
COMPLETED254 Analytics
PHASE3COMPLETED
Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 mg/Day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder
DepressionUnlock trial analytics
PHASE3COMPLETED
Study to Evaluate the Efficacy and Safety of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder
DepressionUnlock trial analytics
PHASE3COMPLETED
A Study to Evaluate the Efficacy and Safety of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder
DepressionUnlock trial analytics
PHASE3COMPLETED
Study of the Effect of Armodafinil Treatment in Healthy Subjects With Excessive Sleepiness Associated With Jet Lag Disorder
Excessive SleepinessUnlock trial analytics
PHASE3COMPLETED
Study to Assess Patient Reported Outcomes With Armodafinil Treatment for Excessive Sleepiness in Adults With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome
Excessive Daytime SleepinessUnlock trial analytics
PHASE3COMPLETED
Safety and Efficacy Study of Armodafinil (CEP-10953) in the Treatment of Excessive Sleepiness Associated With Narcolepsy
NarcolepsyUnlock trial analytics
PHASE3COMPLETED
Safety/Efficacy Study With Armodafinil (CEP-10953) in Treatment of Excessive Sleepiness Associated With Chronic SWSD
Excessive SleepinessUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline to Week 8 in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
Day 0 (baseline), Week 8

The IDS-C30 is a standardized 30-item, clinician-rated scale to assess the severity of a participant's depressive symptoms. Every effort was made to have the same rater evaluate a participant across all visits. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression.

Mean Sleep Latency (Minutes) From the Multiple Sleep Latency Test (MSLT)- Average of Four Scheduled Naps Across Days 1 and 2
Days 1 and 2

MSLT is an assessment that measures likelihood of falling asleep. Mean Sleep Latency measures the time to fall asleep. On Treatment Days 1 and 2 the subject was instructed on 4 occasions to attempt to fall asleep. Each MSLT nap continued until 3 consecutive 30-second epochs of stage 1 sleep were reached, or any 30 second epoch of stage 2, 3, 4 or rapid eye movement sleep was reached. Each nap was terminated after 20 minutes if no sleep occured. Average sleep latency for the 4 naps was tabulated across days 1 and 2. Sleep latency was measured from lights out to first epoch scored as sleep.

Average of Patient Global Impression of Severity (PGI-S) of General Condition Ratings Across Days 1 and 2
Days 1 and 2

The PGI-S rating scale is the patient's assessment of their general condition. The subject rates their overall condition according to the 7 following categories: 1=normal (no sign of illness), 2=borderline ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, and 7=among the most extremely ill. The term "ill" refers here to any symptoms of jet lag and overall feeling. Symptoms may include sleepiness, irritability, malaise, gastrointestinal disturbance, and level of performance. The average of PGI-S ratings across days 1 and 2 are presented here.

Number of Responders to the Patient Global Impression of Change (PGI-C) Ratings
Weeks 4, 8, and 12, at 3 month intervals thereafter, and at a Final Visit (or last postbaseline observation). Evaluation continues until the Final Visit, which occurs when the product is commercially available or the marketing application is withdrawn.

A subjective measure (PGI-C rating) of the patient's global health, ie, a patient's rating of disease severity, as compared with a pretreatment (baseline) evaluation assessment by the patient using the Patient Global Impression of Severity of illness (PGI-S). Responders at each visit were defined as having at least minimal improvement in the severity of excessive sleepiness as compared with a pretreatment evaluation made using the PGI-S.

Change From Baseline in Maintenance of Wakefullness Test (MWT) Score at 12 Weeks
change from baseline at 12 weeks

The Maintenance of Wakefulness Test (MWT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. The change from baseline in the mean sleep latency from the MWT (average of 4 tests at 0900, 1100, 1300, and 1500) was analyzed at weeks 4, 8, and 12. The primary efficacy variable was the mean change from the baseline assessment in MWT sleep latency as assessed at week 12 (or last post-baseline visit).

Change From Baseline in Clinical Global Impression of Change (CGI-C) Score at 12 Weeks
change from baseline at 12 weeks

Number of participants who had at least minimal improvement in CGI-C ratings at Week 12 or last post-baseline visit. The CGI-C uses the following categories and scoring assignments: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; and 7=Very much worse. Severity of illness was assessed at baseline by the CGI-S, which consists of the following categories: 1=Normal (shows no signs of illness); 2=Borderline ill; 3=Mildly (Slightly) ill; 4=Moderately ill; 5=Markedly ill; 6=Severely ill; and 7=Among the most extremely ill patients.

Multiple Sleep Latency Test (MSLT)
up to 12 weeks

The Multiple Sleep Latency Test (MSLT) is an objective assessment of sleepiness that measures the ability of a subject to remain awake. Long latencies to sleep are indicative of a patient's ability to remain awake. Mean sleep latency from MSLT was measured for five 20-minute (maximum) MSLT naps performed at scheduled visits (2400 \[midnight\], 0200, 0400, 0600, and 0800).The MSLT was administered at weeks 4, 8, and 12. The primary efficacy variable was the mean change from the baseline assessment in MSLT sleep latency as assessed at week 12 (or last postbaseline visit).

Clinical Global Impression of Change (CGI-C)
up to 12 weeks

Number of participants who had at least minimal improvement in CGI-C ratings at Week 12 or last post-baseline visit. The CGI-C uses the following categories and scoring assignments: 1=Very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; and 7=Very much worse. Severity of illness was assessed at baseline by the CGI-S, which consists of the following categories: 1=Normal (shows no signs of illness); 2=Borderline ill; 3=Mildly (Slightly) ill; 4=Moderately ill; 5=Markedly ill; 6=Severely ill; and 7=Among the most extremely ill patients.

Mean Change in Negative Scale Scores From the Positive and Negative Syndrome Scale (PANSS) From Baseline to Endpoint
Baseline and Endpoint (Week 24 or last observation after baseline)

PANSS rates severity of psychopathology in schizophrenics. 7 items measure NEGATIVE symptoms: blunted affect, social withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. Each item is scored on a 7-point severity scale: 1=absent, 2=minimal, 3=mild, 4=moderate, 5=moderate severe, 6=severe, 7=extreme. Negative Scale score ranges from 7-49 (higher more severe). Data represents change in Negative Rating Scale from baseline to endpoint with positive scores indicating more severe pathology.

Mean Change From Baseline to Last Observation After Baseline in Composite Score on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery
Baseline and 4 weeks (or last observation after Baseline)

The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score, where the mean is 50 and a standard deviation is 10 for the composite. The data here represents the change from baseline to last observation after baseline in Composite T-Score.

The Mean Change From Baseline to Endpoint (Week 8 or Last Observation After Baseline) in the 30 Item Inventory of Depressive Symptomatology Clinician Rated (IDS C30)
Baseline and 8 weeks from start of study drug administration (or last observation after baseline)

The IDS C30 is a standardized 30 item, clinician rated scale to assess the severity of a patient's depressive symptoms. The scale uses the 9 symptom domains of the DSM-IV criteria to measure symptom severity. The scores range from a minimum of 0 to a maximum score of 84. The higher the score the more severe the symptoms of depression. The data presented here summarizes the change from baseline to Endpoint (either week 8 or the last observation after baseline) in the total score of the IDS-C30.

Maximum observed plasma drug concentration (Cmax) by inspection
Day 1 + up to 72 hours after administration
Time to maximum observed plasma drug concentration (tmax) by inspection
Day 1 + up to 72 hours after administration
Area under the plasma drug concentration by time curve from time 0 to infinity
Day 1 + up to 72 hours after administration
Area under the plasma drug concentration by time curve from time 0 to the time of the last measurable drug concentration
Day 1 + up to 72 hours after administration
Terminal half-life
Day 1 + up to 72 hours after administration
Terminal elimination rate constant
Day 1 + up to 72 hours after administration
Apparent total plasma clearance
Day 1 + up to 72 hours after administration
Apparent volume of distribution
Day 1 + up to 72 hours after administration
Predicted accumulation ratio
Day 1 + up to 72 hours after administration
Maximum observed plasma drug concentration (Cmax)
Day 42 + up to 72 hours after administration
Time to maximum observed plasma drug concentration
Day 42 + up to 72 hours after administration
AUC over 1 dosing interval
Day 42 + up to 72 hours after administration
AUC 0-t
Day 42 + up to 72 hours after administration
Observed accumulation ratio
Day 42 + up to 72 hours after administration
Steady-state accumulation ratio
Day 42 + up to 72 hours after administration

Secondary Endpoints

Percentage of Responders At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)
Percentage of Participants in Remission At Different Treatment Weeks According to the 30-Item Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) Total Score
Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)
Change From Baseline to Different Treatment Weeks in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)
Day 0 (baseline), Weeks 1, 2, 4, 6, 7, and 8, and last postbaseline observation (up to 8 weeks)
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
PlaceboPLACEBO_COMPARATORParticipants began taking placebo to match armodafinil and following the same titration procedure. Treatment was administered for a total of 8 weeks.
Armodafinil 150 mg/dayEXPERIMENTALParticipants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. Treatment was administered for a total of 8 weeks.
Armodafinil 200 mg/dayEXPERIMENTALParticipants started the study at a dose of 50mg/day of armodafinil and titrated up in the first week to 200 mg/day. The 200 mg/day dosage was continued for 7 more weeks for a total of 8 weeks of treatment. This treatment arm was discontinued via a protocol amendment.
1EXPERIMENTALarmodafinil - dosage of 50 mg/day
2EXPERIMENTALarmodafinil - dosage of 150 mg/day
3PLACEBO_COMPARATORmatching placebo
150 mg/day armodafinilACTIVE_COMPARATORAt the baseline visit, patients were randomly assigned to 1 of 3 armodafinil treatment groups or to the placebo treatment group. Patients took 5 tablets orally each day, once daily in the morning. Study drug was titrated (using blister cards) during the double-blind treatment period starting with 50 mg/day of armodafinil or matching placebo. The dosage of armodafinil or matching placebo tablet was increased, as applicable, by 50 mg/day on days 2, 4, 6, and 8, up to the randomized dosage of 150, 200, or 250 mg/day. Patients remained at their randomized dosage for the duration of the study.
200 mg/day armodafinilACTIVE_COMPARATORAt the baseline visit, patients were randomly assigned to 1 of 3 armodafinil treatment groups or to the placebo treatment group. Patients took 5 tablets orally each day, once daily in the morning. Study drug was titrated (using blister cards) during the double-blind treatment period starting with 50 mg/day of armodafinil or matching placebo. The dosage of armodafinil or matching placebo tablet was increased, as applicable, by 50 mg/day on days 2, 4, 6, and 8, up to the randomized dosage of 150, 200, or 250 mg/day. Patients remained at their randomized dosage for the duration of the study.
250 mg/day armodafinilACTIVE_COMPARATORAt the baseline visit, patients were randomly assigned to 1 of 3 armodafinil treatment groups or to the placebo treatment group. Patients took 5 tablets orally each day, once daily in the morning. Study drug was titrated (using blister cards) during the double-blind treatment period starting with 50 mg/day of armodafinil or matching placebo. The dosage of armodafinil or matching placebo tablet was increased, as applicable, by 50 mg/day on days 2, 4, 6, and 8, up to the randomized dosage of 150, 200, or 250 mg/day. Patients remained at their randomized dosage for the duration of the study.
Matching PlaceboPLACEBO_COMPARATORAt the baseline visit, patients were randomly assigned to 1 of 3 armodafinil treatment groups or to the placebo treatment group. Patients took 5 tablets orally each day, once daily in the morning. Study drug was titrated (using blister cards) during the double-blind treatment period starting with 50 mg/day of armodafinil or matching placebo. The dosage of armodafinil or matching placebo tablet was increased, as applicable, by 50 mg/day on days 2, 4, 6, and 8, up to the randomized dosage of 150, 200, or 250 mg/day. Patients remained at their randomized dosage for the duration of the study.
50 mg/day armodafinilACTIVE_COMPARATORArmodafinil or placebo was provided in 50 mg tablet form and subjects were instructed to take 4 tablets orally once daily in the morning. Subjects randomized to the 50 mg/day armodafinil treatment arm for the double-blind treatment period of the study took one 50 mg armodafinil tablet plus three placebo tablets each morning.
100 mg/day armodafinilACTIVE_COMPARATORArmodafinil or placebo was provided in 50 mg tablet form and subjects were instructed to take 4 tablets orally once daily in the morning. Subjects randomized to the 100 mg/day armodafinil treatment arm for the double-blind treatment period of the study took two 50 mg armodafinil tablets plus two placebo tablets each morning. Subjects began taking 50 mg/day and then titrated to 100 mg/day on Day 2 of the first week of the double-blind treatment period.
ArmodafinilACTIVE_COMPARATOR -
Armodafinil 50 mgEXPERIMENTALIn period 1, patients will receive a single 50-mg dose of armodafinil on day 1. In period 2, patients will receive a single 50-mg dose daily on days 1 through 42.
Armodafinil 100 mgEXPERIMENTALIn period 1, patients will receive a single 100 mg dose of armodafinil on day 1. In period 2, patients will receive a single 50-mg dose on day 1 then daily 100-mg doses on days 2 through 42.
Armodafinil 150 mgEXPERIMENTALIn period 1, patients will receive a single 150-mg dose of armodafinil on day 1. In period 2, patients will receive a single 50-mg dose on day 1, 100-mg doses on days 2 and 3, then daily 150-mg doses on days 4 through 42.

Interventions

NameTypeDescription
ArmodafinilDRUGArmodafinil tablets, taken orally, once daily in the morning
PlaceboDRUGMatching placebo tablets, taken orally, once daily in the morning
Armodafinil 150 mg/dayDRUGArmodafinil 150 mg taken 30 minutes to 1 hour before the start of the night shift, but no later than 2300, only on nights worked.
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Eligibility Criteria

Age Range18 Years to 65 Years
SexALL
Healthy VolunteersNo
Study Sites130

Inclusion Criteria: * The patient has a diagnosis of bipolar I disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision) (DSM-IV-TR) criteria and is currently experiencing a major depressive episode. * Documentation that the patient has had at least...

Countries:United StatesArgentinaBrazilBulgariaCroatiaFinlandGermanyHungaryItalyPolandSerbiaSlovakiaSouth AfricaUkraineAustraliaCanadaFranceSpainRomania
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Frequently asked questions about Armodafinil

What is Armodafinil used for?

Armodafinil is an investigational small molecule being studied for use in bipolar I depression, obstructive sleep apnea, excessive sleepiness, schizophrenia, depression, and excessive daytime sleepiness. It is being developed by Teva Pharmaceutical Industries Limited (TEVA) and is currently in Phase 2 clinical development.

What does Armodafinil target?

Armodafinil is a small molecule that targets the central nervous system to promote wakefulness. It is being studied for its effects on excessive sleepiness associated with conditions like obstructive sleep apnea and as an adjunctive treatment for depression in bipolar I disorder.

Who makes Armodafinil?

Armodafinil is being developed by Teva Pharmaceutical Industries Limited, a company traded on the stock exchange under the ticker symbol TEVA. The drug is currently in Phase 2 clinical trials for psychiatric and sleep-related indications.

What phase is Armodafinil in?

Armodafinil is currently in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. Clinical trials have been completed for conditions such as obstructive sleep apnea and bipolar I depression, but the drug remains under investigation.

What clinical trials is Armodafinil in?

Armodafinil has been studied in several completed clinical trials, including NCT00078325 for excessive sleepiness in obstructive sleep apnea, and NCT01072630, NCT01072929, and NCT01305408 for adjunctive treatment of major depression in bipolar I disorder. These trials were randomized, double-blind, and placebo-controlled.

Is Armodafinil the same as Nuvigil?

Armodafinil is the generic name for the drug marketed as Nuvigil. It is the longer-acting enantiomer of modafinil and is used to improve wakefulness in patients with excessive sleepiness associated with conditions like obstructive sleep apnea.