Evaluation of ALKS 2680 for Safety and Efficacy in Treating Excessive Daytime Sleepiness in Narcolepsy Type 2: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2024-515452-20-00
- Protocol
- ALKS 2680-202
- Sponsor
- Alkermes Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of ALKS 2680 for the treatment of excessive daytime sleepiness (EDS) in subjects with Narcolepsy Type 2 (NT2). This is clinically relevant as EDS significantly impacts the quality of life and daily functioning of individuals with NT2, and effective management of this symptom is crucial for improving patient outcomes.
Secondary objectives include:
- Evaluating the efficacy of ALKS 2680 for the treatment of EDS in subjects with NT2.
- Assessing the **safety** and tolerability of ALKS 2680 in subjects with NT2.
Participants
The clinical trial involves a total of **142 participants** diagnosed with **Narcolepsy Type 2**. The study population includes both male and female subjects, aged between **18 to 70 years**, who are experiencing excessive daytime sleepiness (EDS) associated with their condition. Participants were selected based on specific inclusion criteria, including a **Body Mass Index (BMI)** ranging from 18 to 40 kg/m² and a history of unsatisfactory response or side effects from current narcolepsy medications. The trial population is required to adhere to certain lifestyle considerations, such as maintaining consistent use of primary therapy for obstructive sleep apnea (OSA) if applicable, and compliance with actigraphy and diary requirements. The study also includes individuals from vulnerable populations, ensuring a comprehensive evaluation of the efficacy of ALKS 2680 in treating EDS in this demographic. Participants must meet the diagnostic criteria for Narcolepsy Type 2 as per ICSD-3-TR guidelines, confirmed by recent diagnostic evaluations.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of ALKS 2680 in subjects diagnosed with **Narcolepsy Type 2**. This is a Phase II, parallel-group, dose-range-finding study that incorporates randomized, double-blind treatment and open-label periods. The trial aims to assess the change in the mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) from baseline to Week 8, as well as secondary endpoints such as changes in the Epworth Sleepiness Scale (ESS) and the occurrence of treatment-emergent adverse events (TEAEs). The study is expected to commence recruitment on January 15, 2025, and conclude by August 15, 2025.
Participants will be involved in the study for a maximum treatment period of 8 weeks. The trial includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, body mass index (BMI), and previous diagnostic evaluations, followed by regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment. Participants are required to adhere to specific lifestyle considerations and medication restrictions throughout the study duration.
Inclusion criteria stipulate that participants must be between 18 and 70 years of age, have a BMI between 18 and 40 kg/m², and meet the diagnostic criteria for Narcolepsy Type 2 as per ICSD-3-TR guidelines. Exclusion criteria are not explicitly detailed in the provided data. Participants may be withdrawn from the study if they fail to comply with protocol requirements, experience significant adverse effects, or if the investigator deems it necessary for safety reasons.
The investigational product, ALKS 2680, is administered orally in tablet form, with a maximum daily dose ranging from 10 to 18 mg, depending on the specific formulation. A placebo group is included to ensure the validity of the study results. The trial's design and methodology are structured to provide robust data on the safety and efficacy of ALKS 2680 in managing excessive daytime sleepiness (EDS) associated with Narcolepsy Type 2.
Treatment
The clinical trial involves the administration of **ALKS 2680**, a chemical compound developed by Alkermes, Inc. The experimental medication is provided in the form of a **tablet** and is administered **orally**. The study includes three different dosage regimens of ALKS 2680. The first regimen involves a maximum daily dose of **14 mg**, with a total maximum dose of **1414 mg** over a treatment period of 8 weeks. The second regimen allows for a maximum daily dose of **10 mg**, with a total maximum dose of **1190 mg** over the same period. The third regimen permits a maximum daily dose of **18 mg**, with a total maximum dose of **1638 mg**. Each regimen is designed to evaluate the safety and efficacy of ALKS 2680 in subjects with Narcolepsy Type 2 (NT2).
In addition to the experimental medication, a **placebo** is used as a comparator treatment in the study. The placebo is designed to match the appearance of the ALKS 2680 tablets but contains no active substance. The placebo is administered in a manner consistent with the experimental medication to maintain the double-blind nature of the trial. The use of a placebo allows for the assessment of the true efficacy of ALKS 2680 by providing a baseline for comparison.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. This monitoring is crucial for maintaining the integrity of the study data and for accurately assessing the outcomes related to the efficacy and safety of ALKS 2680. The trial is structured to include both randomized double-blind treatment periods and open-label periods, allowing for comprehensive evaluation of the investigational product.
Efficacy
The efficacy of **ALKS 2680** in the treatment of excessive daytime sleepiness (EDS) in subjects with Narcolepsy Type 2 (NT2) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change in the mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) from baseline to Week 8, evaluated by dose level. Secondary endpoints include the change in the Epworth Sleepiness Scale (ESS) score from baseline to Week 8, also assessed by dose level. Additional secondary endpoints involve the evaluation of treatment-emergent adverse events (TEAEs), clinical laboratory assessments, vital signs, safety electrocardiograms (ECGs), and the Columbia-Suicide Severity Rating Scale (C-SSRS) by study period.
These efficacy parameters will be measured and collected at specified timepoints, with the primary and secondary endpoints being assessed at baseline and Week 8. The MWT and ESS are validated tools used to quantify sleep latency and daytime sleepiness, respectively. The analysis of these endpoints will provide insights into the efficacy of ALKS 2680 in managing symptoms of NT2. The study is designed to ensure rigorous assessment of efficacy through these standardized and clinically accepted measures.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Is 18 to 70 years of age at the time of informed consent
- Is willing and able to provide informed consent before study participation, as required by local regulations and IEC requirements
- Has a BMI ≥18 and ≤40 kg/m2 at Visit 1
- In the opinion of the Investigator is experiencing an unsatisfactory clinical response and/or side effect(s) from any medications prescribed for the management of narcolepsy symptoms (including EDS), and can safely discontinue these medications for at least 14 days (or 5 half-lives, whichever is longer) prior to Day 1 and for the duration of study
- Is willing and able, in the opinion of the Investigator, to understand and comply with protocol requirements, including: a. Lifestyle considerations and restrictions detailed in Section 5.3 b. Adherence to contraception guidance detailed in Section 10.4.2 c. Adherence to actigraphy and diary requirements (ie, ≥80% completion) d. If receiving treatment for OSA, adherence to primary OSA therapy over the 30 days prior to Visit 1, and throughout the study, including during overnight visits. Adherence is defined as: − PAP use for ≥4 hours/night on ≥70% of nights (≥5 of 7 nights/week), based on the Investigator’s review of PAP unit data, and ≥4 hours/night during an overnight visit − Oral appliance use on ≥70% of nights (≥5 of 7 nights/week) and during an overnight visit
- Meets the diagnostic criteria of NT2 according to ICSD-3-TR guidelines (Section 10.11), confirmed by the diagnostic evaluations (PSG/MSLT) within the last *5 years. Additionally, meets the following protocol requirements: a. Has residual EDS (ie, ESS total score >12 at Visit 4) b. Has an MSL of ≤15 minutes across the 4 MWT trials during the Screening Period * If the past diagnostic PSG/MSLT was performed >5 years prior to Visit 1, or is otherwise not available, a repeat confirmatory assessment may be conducted by the study site during the Screening Period with the Sponsor’s prior authorization.
Exclusion Criteria
- Has poorly controlled and clinically significant sleep-disordered breathing, at the most recent diagnostic PSG or at Visit 4 (in accordance with the AASM Scoring Manual [rule 1B]): a. Has AHI ≥15 per hour b. If receiving treatment for OSA, has an average AHI ≥10 per hour over the 30 days prior to Visit 1 based on the Investigator’s review of PAP unit data c. Has central apnea index >5 per hour
- Has another comorbid sleep disorder or condition that may influence the sleep-wake cycle: a. Has symptoms of narcolepsy secondary to another medical condition (eg, central nervous system injury or lesion, craniopharyngioma, chronic fatigue syndrome) b. Has performed shift work (working nighttime hours) or is experiencing other life activities (eg, insufficient night sleep; consistently caring for a child who wakes in the night) that interfere with regular nighttime sleep in the past 30 days prior to Visit 4 c. Has an implanted hypoglossal nerve stimulation device (eg, the Inspire® Upper Airway Stimulation system) d. Has nicotine dependence that affects sleep (eg, a subject who routinely wakes at night to smoke). See Section 5.3 for restrictions during the study. e. Excessive caffeine use 1 week prior to Visit 4 or anticipated excessive caffeine use during the study, defined as >600 mg/day of caffeine. See Section 5.3 for restrictions during the study
- Has a significant cardiovascular disease during the Screening Period, or within the last 2 years, including: a. Myocardial infarction, ischemic heart disease, cardiac failure, or arrhythmia b. Atrial fibrillation or an abnormal ECG demonstrating clinically significant dysrhythmia(s), including having a corrected QTcF >450 msec if male and >470 msec if female. Left bundle branch block is not exclusionary if it is asymptomatic and is an isolated ECG finding without clinical significance, as determined by the Investigator. c. Idiopathic sinus tachycardia with a resting HR >100 beats per minute, confirmed on repeat testing within 30 minutes d. Uncontrolled hypertension with systolic BP >130 or diastolic BP >90 mm Hg during Visit 1. One retest is allowed. If the retest measurement is >130/90 mm Hg the subject may be rescreened once, but only after their BP has been stabilized and is ≤130/90 mm Hg for at least 30 days. See Section 8.3.4 for details on BP and HR collection.
- Has a major psychiatric or substance use disorder established in accordance with DSM-5, including: a. Disorders of schizophrenia spectrum (ie, schizophrenia, schizophreniform, schizoaffective disorder, acute or chronic psychotic disorder) b. Bipolar disorder c. Current or recent (within the last 6 months) major depressive episode d. Current or past (within the last 2 years) diagnosis of a moderate or severe substance use disorder e. The subject is at a current risk of suicidal behavior; or has a “Yes” to questions 4 or 5 on the C-SSRS and/or had a suicide attempt in the period within 12 months prior to Visit 1 and up to and including Visit 4
- Has a positive alcohol breath test or urine drug screen for drugs of potential abuse at Visit 4. See Section 10.2 for details.
- Has a history or presence at Visit 1 of other clinically significant (treated or untreated) illness, disease, abnormality, or surgical procedure that, in the opinion of the Investigator, might compromise subject safety, interfere with any study assessment, or affect the subject’s ability to complete the study. This includes but is not necessarily limited to the following: a. Uncontrolled or unstable hypothyroidism or diabetes mellitus b. Clinically significant hepatic or renal disease c. Significant neurological disorder, including dementia, neurodegeneration, stroke, epilepsy, or seizures (excluding pediatric febrile seizures) d. Clinically significant findings on the baseline eye and vision examination (Section 8.3.2.1), or anticipated vision loss or eye surgery during the study
- Presence of the following laboratory abnormalities at Visit 1 (one repeat is allowed at the Investigator’s discretion), including: a. Elevated liver function tests (ALT, AST) >1.5 times the upper limit of normal b. Positive serology test for HBsAg, hepatitis C antibody confirmed by RNA testing at Visit 1 c. Renal creatinine clearance (Cockcroft-Gault Equation) is ≤50 mL/min d. HbA1c ≥6.5%
- Is currently taking (or is anticipated to take) any prohibited prescription or OTC medications listed in Section 5.3, or will not be able to comply with provided washout requirements
- Is currently pregnant, breastfeeding, or is planning to become pregnant during the study
- Is currently enrolled in another clinical study or used any investigational drug or device within 30 days prior to Visit 1
- Is employed by Alkermes, the CRO, or study site (permanent, temporary contract worker, or designee responsible for the conduct of the study) or is immediate family (ie, a spouse, parent, sibling, or child, whether biological or legally adopted) of an Alkermes, CRO, or study site employee
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 15 Jan 2025 | 30 |
 Czechia | Not Recruiting | 15 Jan 2025 | 10 |
 France | Not Recruiting | 15 Jan 2025 | 9 |
 Italy | Not Recruiting | 15 Jan 2025 | 40 |
 The Netherlands | Not Recruiting | 15 Jan 2025 | — |
 Spain | Not Recruiting | 15 Jan 2025 | 25 |
| Netherlands | — | — | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo to match ALKS 2680 | Placebo | N/A | — | — | — | N/A |
ALKS 2680 | Test | TABLET | ORAL | 14 | 8 | PRD11446358 |
ALKS 2680 | Test | TABLET | ORAL | 18 | 8 | PRD11446359 |
ALKS 2680 | Test | TABLET | ORAL | 10 | 8 | PRD11145919 |