Quillivant XR for ADHD in Down Syndrome
(TEAM-DS Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen ByAnna Esbensen, PhD
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Children's Hospital Medical Center, Cincinnati
Must not be taking: ADHD stimulants, MAOIs
Disqualifiers: Psychoses, Bipolar, Organic brain injury, Heart conditions, Severe OSA, Pregnancy, others
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?Children with Down syndrome (DS) have a 3-5 time greater prevalence of Attention Deficit Hyperactivity Disorder (ADHD) than typically developing (TD) children. Despite this higher risk of ADHD, rates of stimulant medication treatment are disproportionately low in children with DS+ADHD, even though stimulants are the most efficacious ADHD treatment and are recommended by consensus guidelines for use in children with intellectual disability and ADHD.
The investigators propose the first randomized clinical trial (RCT) of stimulant medication in children with DS+ADHD. This RCT may provide evidence regarding the short- and long-term safety and efficacy of stimulant use in children with DS+ADHD, both with and without CHD. All children enrolled in the study will complete a comprehensive assessment battery evaluating ADHD diagnostic criteria, as well as behavioral, cognitive, academic, and functional impairments.
Will I have to stop taking my current medications?
If you are currently taking ADHD stimulant or non-stimulant medication, you will need to stop for at least 3 days before starting the study. If you are on a stable dose of non-ADHD, non-MAO psychotropic medication, you can continue as long as there have been no dose changes for at least 4 weeks before the study.
What data supports the effectiveness of the drug Quillivant XR for ADHD in Down Syndrome?
Quillivant XR, a long-acting form of methylphenidate, has been shown to effectively reduce symptoms of ADHD by increasing certain brain chemicals. It is particularly useful for those who have difficulty swallowing pills, offering similar benefits to other ADHD medications.
12345Is Quillivant XR safe for use in humans?
Quillivant XR, a form of methylphenidate, has been studied for safety in treating ADHD. Common side effects include decreased appetite, weight loss, trouble sleeping, high blood pressure, and mood changes, which are consistent with known effects of methylphenidate.
25678How is Quillivant XR different from other ADHD drugs?
Quillivant XR is unique because it is the first long-acting liquid form of methylphenidate, making it easier for people who have trouble swallowing pills to take their medication. It provides a consistent release of the drug throughout the day, reducing the need for multiple doses and potentially improving adherence to treatment.
12359Eligibility Criteria
This trial is for children aged 6 to 17 with Down syndrome and ADHD who can take oral medication, speak English, and meet specific ADHD criteria. They must be willing to follow the study plan and not have brain injuries, severe sleep apnea, certain heart conditions, or be on current ADHD meds they can't stop.Inclusion Criteria
Stated willingness to comply with all study procedures and availability for the duration of the study
You show signs of ADHD, such as being very active, having trouble paying attention, or showing a combination of these behaviors during the KSADS evaluation.
I can take medicine by mouth.
+3 more
Exclusion Criteria
You are allergic to methylphenidate or any of the ingredients in the medication, like banana.
I am taking ADHD medication and cannot stop it for 3 days before the study.
I am currently adjusting doses for my non-ADHD mental health medication.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Baseline Assessment
Baseline intelligence, diagnostic, behavioral, cognitive, health, and functioning assessments
1 week
1 visit (in-person)
Phase 1: Titration
Participants begin the lowest dose of MPH and titrate incrementally upward; biweekly diagnostic and health assessments
6 weeks
6 visits (in-person)
Phase 2: Randomization
Participants randomized to receive optimal dose of MPH or placebo; repeat of baseline measures
2 weeks
1 visit (in-person)
Phase 3: Crossover
Participants crossover to the study intervention not previously assigned; repeat of assessments
2 weeks
1 visit (in-person)
Phase 4: Open-label Maintenance
Participants undergo an open label trial with their optimal MPH dose for a four-month maintenance period; monthly assessments
16 weeks
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
1 visit (in-person)
Participant Groups
The trial tests Quillivant XR (a stimulant medication) against a placebo in children with Down syndrome who also have ADHD. It's designed to see if this medicine is safe and works well over both short and long terms compared to no active treatment.
2Treatment groups
Active Control
Placebo Group
Group I: Quillivant XRActive Control1 Intervention
Once-daily, long-lasting MPH solution with the following dosing schedules: 7.5mg/15mg/22.5mg/30mg for children 20-25kg 10mg/20mg/30mg/40mg for children 26-30kg 10mg/22mg/34mg/46mg for children \> 30 mg
Group II: PlaceboPlacebo Group1 Intervention
Liquid-based suspension to match the color and banana-flavor of Quillivant XR.
Quillivant XR is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Quillivant XR for:
- Attention Deficit Hyperactivity Disorder (ADHD)
🇪🇺 Approved in European Union as Methylphenidate for:
- Attention Deficit Hyperactivity Disorder (ADHD)
🇨🇦 Approved in Canada as Methylphenidate for:
- Attention Deficit Hyperactivity Disorder (ADHD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Boston Children's HospitalBoston, MA
University of Pittsburgh Medical CenterPittsburgh, PA
Cincinnati Children's Hospital Medical CenterCincinnati, OH
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
University of Pittsburgh Medical CenterCollaborator
Boston Children's Hospital, Boston, MA, USACollaborator
University of California, DavisCollaborator
References
New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability. [2018]Psychostimulants are the recommended first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate is one of the most commonly used psychostimulants worldwide. Given that immediate-release and/or tablet/capsule formulations may decrease adherence to methylphenidate treatment, several drug companies have been developing novel long-acting and/or liquid/chewable formulations that may improve adherence as well as (for long-acting formulations) reduce abuse potential, decrease stigma associated with multiple administrations per day, and decrease the potential for adverse effects related to dosage peak. Here, we review the pharmacokinetics, efficacy, and tolerability of novel formulations of methylphenidate that are in development or have been approved by the US FDA or European Medicines Agency (EMA) in the last 5 years. We searched the websites of the FDA, EMA, ClinicalTrials.gov, and the pertinent drug companies. We also searched PubMed, Ovid databases (MEDLINE, PsycINFO, Embase + Embase classic), and ISI Web of Knowledge (Web of Science [Science Citation Index Expanded], Biological Abstracts, Biosis, Food Science and Technology Abstracts) to retrieve any additional pertinent information. We found data from trials for the following compounds: (1) methylphenidate extended-release oral suspension (MEROS; NWP06, Quillivant™); (2) methylphenidate extended-release chewable capsules (NWP09, QuilliChew ER™); (3) methylphenidate hydrochloride extended-release capsules (Aptensio XR™); (4) methylphenidate extended-release orally disintegrating tablets (XR-ODT; NT-0102, Cotempla™); (5) ORADUR technology (once-daily tamper-resistant formulation) methylphenidate sustained release (SR); and (6) methylphenidate modified-release (HLD-200; Bejorna™). Overall, available evidence based on trials suggests these compounds have good efficacy and tolerability. Future research should further explore the effectiveness and tolerability of these new formulations as well as their potential to improve adherence to treatment in the 'real world' via pragmatic trials.
Extended-Release Viloxazine for the Treatment of Attention-Deficit Hyperactivity Disorder in School-Age Children and Adolescents. [2023]To describe the efficacy and safety of extended-release viloxazine (viloxazine ER; Qelbree) for the treatment of attention-deficit hyperactivity disorder (ADHD) in school-age children and adolescents (6-17 years).
Efficacy, Safety, and Tolerability of a Novel Methylphenidate Extended-Release Oral Suspension (MEROS) in ADHD. [2022]To test whether an optimal dose of Quillivant XR (methylphenidate extended-release oral suspension [MEROS]) would significantly reduce symptoms of ADHD in children.
Open-Label Dose Optimization of Methylphenidate Extended-Release Orally Disintegrating Tablet in a Laboratory Classroom Study of Children with Attention-Deficit/Hyperactivity Disorder. [2021]Objective: To examine the efficacy, safety, and tolerability of methylphenidate extended-release orally disintegrating tablets (MPH XR-ODT) for the treatment of attention-deficit/hyperactivity disorder (ADHD) during the open-label dose-optimization/stabilization period of a phase 3 laboratory classroom study. Methods: Children (6-12 years) diagnosed with ADHD were enrolled. Treatment was initiated with MPH XR-ODT 20 mg daily. Doses were adjusted weekly by 10-20 mg during the 4-week dose-optimization period (visits 2-5) until an optimal dose was reached. The optimal dose was sustained during a 1-week stabilization period (visits 6-7). Efficacy was assessed using the ADHD Rating Scale-IV (ADHD-RS-IV) score and the Clinical Global Impression-Improvement (CGI-I) score. Adverse events (AEs) were recorded throughout the study. A secondary subgroup analysis by baseline ADHD-RS-IV score, sex, age, and weight was also performed. Results: The mean (standard deviation [SD]) final optimized MPH XR-ODT daily dose was 41.8 (14.6) mg and ranged from 20 to 60 mg. Final optimized dose was higher for children with more severe baseline ADHD-RS-IV total scores. ADHD-RS-IV total scores decreased progressively during dose optimization, with a mean (SD) change from baseline at visit 7 of -21.4 (8.9). CGI-I scores shifted from "minimally improved" (mean [SD]: 3.1 [1.1]) at visit 3 to "much improved" (1.6 [0.6]) at visit 7. Baseline ADHD-RS-IV total score was highest for participants optimized to 40 mg (mean [standard error]: 40.0 [1.4]) and lowest for those optimized to 20 mg (34.8 [2.1]). By visit 6, mean ADHD-RS-IV score was comparable for all optimized dose groups. Common treatment-emergent AEs (≥5% of participants) included decreased appetite, upper abdominal pain, headaches, and insomnia. Conclusions: Dose optimization of MPH XR-ODT led to a reduction in ADHD symptoms, indicated by a decrease in ADHD-RS-IV and CGI-I scores. AEs were consistent with those of other MPH products. Clinical Trial Registry: NCT01835548 (ClinicalTrials.gov).
The use of methylphenidate hydrochloride extended-release oral suspension for the treatment of ADHD. [2022]More than 50 years ago, methylphenidate immediate-release (MPH-IR) was found to be effective in relieving symptoms of attention-deficit/hyperactivity disorder. Although the exact mechanism of the action is unknown, the efficacy of MPH is thought to be mediated by blocking the reuptake of norepinephrine and dopamine into the presynaptic neuron and increasing the release of these neurotransmitters into the extraneuronal space. Because of its short duration of effect, MPH-IR had to be dosed multiple times daily. In recent years, several methyphenidate extended-release (MPH-ER) formulations have been developed. Methylphenidate hydrochloride for extended-release oral suspension (MEROS or Quillivant(TM) XR) is the first long-acting MPH-ER oral suspension developed to treat attention-deficit/hyperactivity disorder. It offers advantages when compared with other MPH-ER preparations for patients who cannot or prefer not to swallow or manipulate capsules or wear a transdermal patch, while maintaining comparable efficacy and duration of effect. The pharmacokinetic, efficacy and safety profiles of this controlled substance are reviewed.
Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder. [2021]Objectives: To assess the efficacy and safety of a methylphenidate hydrochloride extended-release capsule (MPH-MLR) formulation in treating attention-deficit/hyperactivity disorder (ADHD) in preschool children. Methods: Children aged 4 to <6 years with qualifying ADHD Rating Scale Fourth Edition (ADHD-RS-IV) Preschool Version scores (≥90th percentile for age/gender) participated in four behavior management training (BMT) sessions or immediately entered (based on investigator assessment of symptom severity or previous participation) into a 6-week, open-label, flexible MPH-MLR dose optimization phase. After BMT, children with <30% improvement in ADHD-RS-IV score and ≥3 score on the Clinical Global Impression-Improvement (CGI-I) scale also entered the open-label period. All children began the open-label period with MPH-MLR 10 mg once daily; weekly adjustments permitted once-daily maximum of up to 40 mg. Children with ≥30% improvement in ADHD-RS-IV total score and a CGI-I score of 1-2 at open-label completion were randomized to their optimized dose of MPH-MLR or placebo for 2 weeks (double blind [DB]). Safety measures included adverse events (AEs), vital signs, and electrocardiograms. Results: Open-label enrollment was 119 children. Mean (SD) ADHD-RS-IV total scores at open-label start and open-label end was 40.8 (10.4) and 19.5 (11.1), respectively. Ninety children were enrolled in the DB phase. Mean (SD) ADHD-RS-IV total scores for the MPH-MLR and placebo group were similar at DB beginning and was 25.8 (14.6) and 34.9 (14.1), respectively, at DB end. Mean change from baseline in ADHD-RS-IV total score during DB was significantly greater in children randomized to placebo compared with MPH-MLR; least squares mean change difference from baseline was -11.2, p = 0.002. During open-label dosing, the most common AEs (≥10%) were decreased appetite, decreased weight, insomnia, hypertension, emotional disorder, and affect lability. Conclusion: Results demonstrate MPH-MLR efficacy in preschool children and a safety profile consistent with known AEs of methylphenidate when used for ADHD.
The occurrence of adverse drug reactions reported for attention deficit hyperactivity disorder (ADHD) medications in the pediatric population: a qualitative review of empirical studies. [2021]To review empirical studies of adverse drug reactions (ADRs) reported to be associated with the use of medications generally licensed for treatment of attention deficit hyperactivity disorder (ADHD) symptoms in the pediatric population.
Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder. [2018]This phase 3, laboratory classroom study assessed the efficacy and safety of methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD).
Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study. [2013]The study objectives were to 1) evaluate medication adherence for adults with attention-deficit/hyperactivity disorder (ADHD) treated with 3 times daily (TID) mixed amphetamine salts immediate release (MAS IR) versus once-daily (qAM) MAS extended release (MAS XR) in a randomized, crossover study; and 2) to examine the associations between adherence and efficacy for MAS IR and MAS XR.