Clinical trial NCT04987762
Conditions: Attention Deficit/Hyperactivity Disorder
Keywords: ADHD methylphenidate Adhansia XR Pediatric
Sponsor: Purdue Pharma LP
Start date: 2021-08-03; Completion date: 2022-04-27
Enrollment: 103 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to assess the long-term safety of Adhansia XR in children and to characterize the pharmacokinetics (PK) in 4 to 5 year-olds.

Detailed description:

Arms: arm 1: Adhansia XR capsules taken orally once daily in the morning
Interventions: intervention 1: Adhansia XR
Intervention descriptions: intervention 1: Methylphenidate extended-release capsules taken once daily (12.5 mg, 25 mg, 35 mg, 45 mg, 55 mg, and 70 mg)

Protocol documents:
Prot_SAP_001.pdf: 














Sponsor Name: Purdue Pharma LP 
Protocol Number: ADA4004 
Protocol Version and Date: Version 2,  26 Apr 2021 
Page 8 of 11 
CONFIDENTIAL 
2.
Females of childbearing potential who are not pregnant and not nursing.
3.
Females of childbearing potential who agree to practice a clinically accepted method of
contraception during the study and for at least 1 month prior to study dosing and 1 month
following completion of the study. Acceptable contraceptive methods include abstinence,
oral contraception, surgical sterilization (bilateral tubal ligation, bilateral oophorectomy,
or hysterectomy), intrauterine device, or diaphragm in addition to spermicidal foam and
condom on male partner, or systemic contraception (eg, levonorgestrel-releasing implant).
4.
Diagnosis of ADHD (any type: combined, predominately hyperactive impulsive type or
predominately inattentive type) by a psychiatrist, psychologist, pediatrician, or licensed
allied healthcare professional using the Diagnostic and Statistical Manual of Mental
Disorders (DSM-5) and confirmed by administration of a structured diagnostic interview
using the Kiddie–Schedule for Affective Disorders and Schizophrenia for School Age
Children–Present and Lifetime DSM-5 version (K-SADS-PL).
5.
Subjects who have received, or are receiving treatment with medication (amphetamine,
methylphenidate, or non-stimulant) for ADHD must be willing to undergo a washout
period of a minimum of 3 days or 5 half-lives, whichever is longer, prior to study drug
administration. Some medications may require a washout period greater than 3 days or a
dose taper, depending on the product labeling.
6.
If subjects are currently off treatment, this must be for any reason other than
noncompliance, nonresponse, or intolerance to side effects.
7.
Ratings on the attention deficit/hyperactivity disorder–Rating Scale, version 5
(ADHD-RS-5) when the subject is not receiving treatment for ADHD must be ≥90th
percentile normative value for sex and age in at least 1 of the categories: total score,
inattentive subscale, or hyperactive/impulse subscale.
8.
Dissatisfied with his or her current pharmacological therapy for treatment of ADHD or
not currently receiving pharmacological therapy for ADHD for any reason other than
nonresponse, noncompliance, or tolerability issues with stimulants. Newly diagnosed and
treatment naïve subjects may be included at the discretion of the investigator.
9.
Must be functioning at an age-appropriate level intellectually as determined by an
intelligence quotient (IQ) of ≥80 on a documented IQ assessment such as the Wechsler
Abbreviated Scale of Intelligence II (WASI-II) vocabulary and matrix reasoning
components, or the Kaufman Brief Intelligence Test, Second Edition (KBIT-2).
10. Parent(s)/legal guardian(s) must have the ability to read and understand the language in
which the informed consent is written and are mentally and physically competent to
provide written informed consent for their child.
11. Written or verbal assent from the subject (as applicable).
12. Subject and parent(s)/legal guardian/caregiver are willing and able to comply with all the
protocol requirements and parent(s)/legal guardian/caregiver must be able to provide
transportation for the subject to and from the clinic visits.
Specific inclusion criteria for the PK substudy 
The following additional inclusion criteria must be met for a subject to be eligible for the PK 
substudy: 
13. Male and female subjects ≥4 and <6 years of age at the time of informed consent/assent.
14. BMI within normal range for age (>3rd percentile and <97th percentile).
15. Parent(s)/legal guardian(s)/ caregiver(s) are willing for their child to remain off prescription
or nonprescription medications and over-the-counter preparations (herbal, nutritional


Sponsor Name: Purdue Pharma LP 
Protocol Number: ADA4004 
Protocol Version and Date: Version 2,  26 Apr 2021 
Page 9 of 11 
CONFIDENTIAL 
supplements, vitamin and mineral preparations such as omega-3 fatty acids) for the duration 
of the PK substudy. 
16. Parent(s)/legal guardian(s)/ caregiver(s) must be able to accompany the subject for the
duration of inpatient stay during the PK substudy.
General exclusion criteria 
A subject who meets any of the following exclusion criteria will not be eligible for inclusion in 
the study: 
1.
Has a known allergy, intolerance, or hypersensitivity to methylphenidate.
2.
History of allergic reactions to tartrazine.
3.
Known nonresponder to methylphenidate treatment.
4.
Subject has received a monoamine oxidase inhibitor within 2 weeks before study
treatment.
5.
Blood pressure and heart rate outside the 95th percentile for age and sex.
6.
Subject has a current or recent history (within the past 6 months) of drug abuse or
dependence disorder; or someone in the subject’s immediate family has a current or recent
history (within the past 6 months) of drug abuse or dependence disorder; or someone
living at the subject’s home has a current or recent history (within the past 6 months) of
drug abuse or dependence disorder; or subject has a positive urine drug screen for
stimulant medication (other than currently prescribed stimulant for the treatment of
ADHD) or drugs of abuse at the screening visit.
7.
Has abnormal thyroid function, glaucoma, Gilles de la Tourette’s disorder, a history of
seizures (except simple febrile seizures), or a tic disorder. Mild medication-induced tics
are not exclusionary.
8.
Primary and/or comorbid psychiatric diagnosis other than ADHD with the exception of
simple phobias, motor skill disorders, communication disorders, learning disorders, and
adjustment disorders so long as such disorder is judged not to interfere with study
participation or the safety of the subject.
9.
Subjects with a family history (first-degree relatives) of sudden cardiac death require
review and approval by the medical monitor for participation in the study.
10. Subject has a history of disorders of the sensory organs, including deafness, blindness or
the subject is severely or profoundly developmentally disabled.
11. Any clinically significant abnormality or clinically significant abnormal laboratory test
results found during screening or a positive test for hepatitis A, hepatitis B, hepatitis C, or
HIV found during screening (subjects who have received a hepatitis A vaccine and test
positive for hepatitis A may be included in the study, at the discretion of the investigator).
12. Use of an investigational drug within 30 days (90 days for biologics) or participation in an
investigational study within 30 days prior to dosing.
13. Any reason which, in the opinion of the investigator, would prevent the subject from
participating in the study.
14. Clinically significant ECG abnormalities (including but not limited to Wolff-Parkinson-
White syndrome, supraventricular tachycardia, left ventricular hypertrophy, abnormal
conduction defect, or other cardiac arrhythmia), or vital sign abnormalities (normal vital
signs should be between 5th and 95th percentile for age) at screening.
15. Known history of cardiovascular disorders including hypertension, angina, arterial
occlusive disease, heart failure, hemodynamically significant congenital heart disease,


Sponsor Name: Purdue Pharma LP 
Protocol Number: ADA4004 
Protocol Version and Date: Version 2,  26 Apr 2021 
Page 10 of 11 
CONFIDENTIAL 
cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias, and 
channelopathies (disorders caused by the dysfunction of ion channels). 
16. Clinically significant history of neurological, endocrinal (including thyrotoxicosis),
pulmonary, hematological, immunologic, gastrointestinal, renal, hepatic or metabolic
disease, or psychiatric illness other than ADHD.
17. History of anxiety, tension, agitation, motor tics, Tourette’s syndrome or a family history
(first-degree relatives) of Tourette’s syndrome.
18. History of glaucoma.
19. Has a positive serum pregnancy test (if applicable) at screening.
20. Positive findings on C-SSRS for suicidal ideation or behaviors at screening.
21. Clinically significant illness or surgery within 4 weeks prior to dosing. Subjects who
experience vomiting within 24 hours prior to clinic admission will be carefully evaluated
for upcoming illness/disease.
22. Hemoglobin <105 g/L or hematocrit <0.310 L/L at screening (subjects with abnormal
hemoglobin and/or hematocrit levels deemed not clinically significant may be included in
the study, at the discretion of the investigator).
23. Subject has received anticonvulsants (eg, phenobarbital, phenytoin, primidone), coumarin
anticoagulants, prescription pressor agents, pressor agents, guanethidine, tricyclic
antidepressants (imipramine, desipramine, selective serotonin inhibitors) or herbal
remedies within 30 days prior to the first dosing, or melatonin within 3 days prior to the
first dosing.
Specific exclusion criteria for the PK substudy 
A subject who meets any of the following exclusion criteria will not be eligible for inclusion 
in the PK substudy: 
24. Use of beverages and foods containing grapefruit, caffeine or xanthine within 48 hours
prior to clinic admission for PK blood sample collection. Xanthine containing beverages
or foods are defined as containing caffeine, theophylline or theobromine (eg, coffee, tea,
chocolate, cocoa). Allowance for a single incidental consumption may be evaluated and
approved by the investigator based on the potential for interaction with the study drug.
25. Use of medication other than topical products (without significant systemic absorption):
26. Prescription medication within 3 days prior to the first dosing (excluding subject’s
prestudy ADHD medication)
27. Over-the-counter products within 7 days prior to the first dosing with the exception of the
occasional use of acetaminophen (up to the daily maximum dose recommended for
subject’s age)
Test product: 
Name: Adhansia XR (methylphenidate hydrochloride extended-release capsules) 
Dose: 12.5 (starting dose only for children 4 to less than 6 years of age), 25 (starting dose for 
children 6 to 12 years of age), 35, 45, 55, or 70 mg administered once daily 
Mode of administration: oral 
Statistical methods: 
Analysis datasets