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ALKS 5461

Phase 3

Major Depressive Disorder | Small molecule | Psychiatry |Alkermes plc|Last Updated: Apr 8, 2021

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials8
Total Enrollment3,242

FDA Designations

No designations recorded

Clinical trial landscape

ALKS 5461 · 16 trials · 6 indications

Phase 3 6Phase 2 1Phase 1 9
NCT03188185A Study of ALKS 5461 for Treatment Refractory Major Depressive Disorder (MDD)Major Depressive Disorder
COMPLETED278 Analytics
NCT02218008A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - FORWARD-5 StudyMajor Depressive Disorder
COMPLETED407 Analytics
NCT02141399A Long-Term Safety Study of ALKS 5461Major Depressive Disorder
COMPLETED1,485 Analytics
NCT02158533A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-4 StudyMajor Depressive Disorder
COMPLETED385 Analytics
NCT02158546A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-3 StudyMajor Depressive Disorder
COMPLETED447 Analytics
NCT02085135A Study of Different Titration Schedules of ALKS 5461 in Adults With Major Depressive Disorder (MDD)Major Depressive Disorder
COMPLETED66 Analytics
PHASE3COMPLETED
A Study of ALKS 5461 for Treatment Refractory Major Depressive Disorder (MDD)
Major Depressive DisorderUnlock trial analytics
PHASE3COMPLETED
A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - FORWARD-5 Study
Major Depressive DisorderUnlock trial analytics
PHASE3COMPLETED
A Long-Term Safety Study of ALKS 5461
Major Depressive DisorderUnlock trial analytics
PHASE3COMPLETED
A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-4 Study
Major Depressive DisorderUnlock trial analytics
PHASE3COMPLETED
A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-3 Study
Major Depressive DisorderUnlock trial analytics
PHASE3COMPLETED
A Study of Different Titration Schedules of ALKS 5461 in Adults With Major Depressive Disorder (MDD)
Major Depressive DisorderUnlock trial analytics

Study Endpoints

Primary Endpoints

Change From Baseline to the End of Treatment (EOT) in the Montgomery Asberg Depression Rating Scale-10 (MADRS-10) Scores
Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2

The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of Major Depressive Disorder (MDD) symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.

Change in Montgomery Asberg Depression Rating Scale (MADRS)-6 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)
Baseline and 5 weeks (Stage 1) and baseline and 6 weeks (Stage 2), combined together for the overall estimate of treatment effect

The MADRS-6 scale is a clinician-administered questionnaire used to measure the severity of MDD symptoms. The MADRS-6 scale is a subset of the MADRS-10 scale, comprised of the following individual questionnaire items: Apparent Sadness, Reported Sadness, Inner Tension, Lassitude, Inability to Feel, and Pessimistic Thoughts. Scores range from 0 (no apparent symptoms) to 36 (most severe symptoms).

Change in MADRS-10 Score Using Average of Changes From Baseline to Week 3 Through the End of Treatment Period (Week 5 for Stage 1, Week 6 for Stage 2)
5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)

The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.

Change From Baseline to End of Treatment in the MADRS-10
5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)

The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.

Incidence of Adverse Events (AEs)
Up to 56 weeks
Change From Baseline to Week 5 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score
Baseline and 5 weeks for each stage

The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.

Change From Baseline to End of Treatment (Week 6) in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score
Baseline and week 6

The MADRS-10 scale is a clinician-administered questionnaire comprised of 10 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 60 (most severe symptoms). Individual questionnaire items include: Apparent Sadness, Reported Sadness, Inner Tension, Reduced Sleep, Reduced Appetite, Concentration Difficulties, Lassitude, Inability to Feel, Pessimistic Thoughts, and Suicidal Thoughts.

Number of Subjects With Adverse Events (AEs)
8 weeks
Change From Baseline to Week 4 in Hamilton Rating Scale for Depression (HAM-D17) Total Score
Baseline and 4 weeks for each stage

The HAM-D17 scale is a clinician-administered questionnaire comprised of 17 items used to measure the severity of MDD symptoms. Scores range from 0 (no apparent symptoms) to 50 (most severe symptoms). Individual questionnaire items include depressed mood, work and activities, insomnia (early), insomnia (middle), insomnia (late), genital symptoms, somatic symptoms (gastrointestinal), loss of weight, somatic symptoms (general), feelings of guilt, suicide, anxiety (psychic), anxiety (somatic), hypochondriasis, insight, agitation, and retardation.

Area under the plasma concentration versus time curve from time 0 to infinity (AUC0-inf) following a single dose of ALKS 5461
up to 168 hours postdose
Area under the plasma concentration versus time curve from time 0 to time of last measurable concentration (AUC0-last) following a single dose of ALKS 5461
up to 168 hours postdose
Maximum observed plasma concentration (CMAX) following a single dose of ALKS 5461
up to 168 hours postdose
AUCinf
Up to 72 hours

Area under the plasma concentration-time curve from time 0 to infinity for ALKS 5461

AUClast
Up to 72 hours

Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration for ALKS 5461

Cmax
Up to 72 hours

Maximum observed plasma concentration for ALKS 5461

Change in QT interval corrected for heart rate using the Fridericia formula (QTcF)
Up to 14 days
Area under the plasma concentration versus time curve from time 0 to time of last measureable concentration (AUC0-last) following a single dose of ALKS 5461
Up to 168 hours postdose
Pharmacodynamics: Abuse potential measured by visual analog scales (VAS)
Approximately 14 weeks
Drug-Drug Interaction - AUC0-t
Up to 48 hours

Area under the concentration time curve from time zero to the last measureable time point (AUC0-t) of ALKS 5461 in the presence and absence of itraconazole

Drug-Drug Interaction - AUC0-inf
Up to 48 hours

Area under the concentration time curve from time zero to infinity (AUC0-inf) of ALKS 5461 in the presence and absence of itraconazole

Drug-Drug Interaction - Cmax
Up to 48 hours

Maximum plasma concentration (Cmax) of ALKS 5461 in the presence and absence of itraconazole

Relative bioavailability of ALKS 5461 treatment groups
21 days

The parameters for determining the bioavailability include Cmax, AUC last, and AUC(0-infinity).

The number and percent of subjects with treatment-emergent adverse events following sublingual administration of ALKS 33 and buprenorphine co-formulation (ALKS 5461)
7 days

Measured over a range of dose levels in subjects with inadequate/partial response to antidepressant therapy during the current episode of MDD.

Secondary Endpoints

Montgomery Asberg Depression Rating Scale (MADRS) Response Rate
Baseline and 5 weeks for Stage 1, Baseline and 6 weeks for Stage 2
Montgomery Asberg Depression Rating Scale (MADRS) Remission Rate
5 weeks for Stage 1, 6 weeks for Stage 2
Proportion of Patients Who Exhibited Treatment Response (MADRS-10)
5-6 Weeks (5 weeks for Stage 1 and 6 weeks for Stage 2)
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
ALKS 5461EXPERIMENTALSublingual tablets
ALKS 5461 PlaceboPLACEBO_COMPARATORSublingual tablets
High DoseEXPERIMENTAL -
Low DoseEXPERIMENTAL -
PlaceboPLACEBO_COMPARATOR -
Titration Schedule 1EXPERIMENTAL -
Titration Schedule 2EXPERIMENTAL -
MoxifloxacinACTIVE_COMPARATOROral tablet
ALKS 5461 Dose 1EXPERIMENTALSublingual tablets
ALKS 5461 Dose 2EXPERIMENTALSublingual tablets
ALKS 5461 Dose 3EXPERIMENTALSublingual tablets
Buprenorphine Dose 1ACTIVE_COMPARATORSublingual tablets
Buprenorphine Dose 2ACTIVE_COMPARATORSublingual tablets
ItraconazoleOTHERItraconazole or placebo
ALKS 5461-AEXPERIMENTAL -
ALKS 5461-BEXPERIMENTAL -
ALKS 5461 (ALKS 33 and buprenorphine)EXPERIMENTAL -

Interventions

NameTypeDescription
ALKS 5461DRUGSamidorphan + buprenorphine, administered sublingually
ALKS 5461 PlaceboDRUGPlacebo tablet, administered sublingually
PlaceboDRUGSublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
High Dose ALKS 5461DRUGSublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
Low Dose ALKS 5461DRUGSublingual tablet, taken once daily (in addition to open-label treatment with a commercially available antidepressant)
MoxifloxacinDRUGSingle administration
BuprenorphineDRUGSublingual tablets, single administration
ItraconazoleDRUGAdministered orally in a crossover design
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Eligibility Criteria

Age Range18 Years to 70 Years
SexALL
Healthy VolunteersNo
Study Sites35

Inclusion Criteria: * Have a Major Depressive Disorder (MDD) primary diagnosis * Have a body mass index (BMI) of 18.0 to \</= 40.0 kg/m\^2 * Be willing and able to follow the study procedures and visits as outlined in the protocol (including agreeing not to enroll in any other clinical trials) * Ha...

Countries:United StatesAustraliaPuerto RicoCanadaGermanyBulgariaHungaryPoland
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Frequently asked questions about ALKS 5461

What is ALKS 5461 used for?

ALKS 5461 is an investigational small molecule being studied for use in Major Depressive Disorder (MDD). It has also been evaluated in clinical trials involving healthy volunteers, pharmacokinetics, renal impairment, and hepatic impairment. The drug is being developed by Alkermes plc and is currently in Phase 1 clinical development.

Who makes ALKS 5461?

ALKS 5461 is being developed by Alkermes plc, a biopharmaceutical company traded on the NASDAQ under the ticker symbol ALKS. The company is conducting clinical trials to evaluate the drug's safety, tolerability, and pharmacokinetics in various patient populations, including those with Major Depressive Disorder.

What phase is ALKS 5461 in?

ALKS 5461 is currently in Phase 1 clinical development. While some earlier studies have been completed, the drug remains investigational and has not been approved by regulatory authorities. It is being studied for its potential use in treating Major Depressive Disorder and for pharmacokinetic evaluation in special populations.

What clinical trials is ALKS 5461 in?

ALKS 5461 has been studied in several completed clinical trials. These include NCT01381107, a Phase 1 safety and tolerability study in subjects with Major Depressive Disorder; NCT01500200, a Phase 2 study in MDD; NCT02452801, a pharmacokinetics study in hepatic impairment; and NCT02545439, a drug-drug interaction study in healthy volunteers.

Is ALKS 5461 the same as ALKS 33-BUP?

Yes, ALKS 5461 is also known as ALKS 33-BUP. The drug has been referred to by this alternative name in clinical trial documentation, such as in the study titled 'ALK33BUP-201: Safety and Tolerability Study of ALKS 33-BUP (ALKS 5461) Administration in Subjects With MDD.' Both names refer to the same investigational compound.