Trial Outcomes & Findings for Pharmacokinetics of HLD200 in Children and Adolescents With ADHD (NCT NCT01907360)
NCT ID: NCT01907360
Last Updated: 2021-12-23
Results Overview
The absorption lag time for methylphenidate in plasma expressed in hours is the difference in time between the drug administration and the last time point where the drug concentration was below the limit of assay quantitation.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
29 participants
Primary outcome timeframe
48hrs
Results posted on
2021-12-23
Participant Flow
A total of 29 subjects were enrolled (18 adolescents and 11 children in sequential cohorts). Following consent/assent and screening procedures, subjects were required to wash-out of all ADHD medications for 5 days prior clinic admission for testing.
Participant milestones
| Measure |
Adolescents (13-17yrs)
Drug: B-HLD200 54mg capsules (Methylphenidate Modified Release B Formulation) or Drug: C-HLD200 54mg capsules (Methylphenidate Modified Release C Formulation)
B-HLD200 54mg capsules
C-HLD200 54mg capsules
|
Children (6-12 Yrs)
Drug: B-HLD200 54mg capsules (Methylphenidate Modified Release B Formulation) or Drug: C-HLD200 54mg capsules (Methylphenidate Modified Release C Formulation)
B-HLD200 54mg capsules
C-HLD200 54mg capsules
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
11
|
|
Overall Study
COMPLETED
|
18
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics of HLD200 in Children and Adolescents With ADHD
Baseline characteristics by cohort
| Measure |
HLD200 (Methylphenidate Hydrochloride) in Adolescents
n=18 Participants
HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to adolescents aged 13-17 years.
|
HLD200 (Methylphenidate Hydrochloride) in Children
n=11 Participants
HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 6-12 years.
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
15.4 years
STANDARD_DEVIATION 1.24 • n=93 Participants
|
10.5 years
STANDARD_DEVIATION 1.37 • n=4 Participants
|
13.52 years
STANDARD_DEVIATION 2.75 • n=27 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
19 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Height (cm)
|
169.56 cm
STANDARD_DEVIATION 6.487 • n=93 Participants
|
143.18 cm
STANDARD_DEVIATION 6.072 • n=4 Participants
|
159.55 cm
STANDARD_DEVIATION 14.434 • n=27 Participants
|
|
Weight (kg)
|
67.71 kg
STANDARD_DEVIATION 14.588 • n=93 Participants
|
36.08 kg
STANDARD_DEVIATION 7.950 • n=4 Participants
|
54.74 kg
STANDARD_DEVIATION 19.704 • n=27 Participants
|
PRIMARY outcome
Timeframe: 48hrsPopulation: All enrolled subjects included in analysis population.
The absorption lag time for methylphenidate in plasma expressed in hours is the difference in time between the drug administration and the last time point where the drug concentration was below the limit of assay quantitation.
Outcome measures
| Measure |
HLD200 in Adolescents (13-17 Years)
n=18 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54 mg) capsules
|
HLD200 in Children (6-12 Yrs)
n=11 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54mg) capsules
|
|---|---|---|
|
PK Parameters for Rate and Extent of Absorption of MPH: Lag Time
|
6.3 hours
Standard Deviation 1.3
|
3.3 hours
Standard Deviation 2.7
|
PRIMARY outcome
Timeframe: 48hrsPopulation: All enrolled subjects included in analysis population.
The maximum drug concentration of methylphenidate in plasma.
Outcome measures
| Measure |
HLD200 in Adolescents (13-17 Years)
n=18 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54 mg) capsules
|
HLD200 in Children (6-12 Yrs)
n=11 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54mg) capsules
|
|---|---|---|
|
PK Parameters for Rate and Extent of Absorption of MPH: Cmax
|
7.17 ng/mL
Standard Deviation 1.7
|
11.64 ng/mL
Standard Deviation 4.2
|
PRIMARY outcome
Timeframe: 48hrsPopulation: All enrolled subjects included in analysis population.
The time to reach maximum concentration of methylphenidate in plasma.
Outcome measures
| Measure |
HLD200 in Adolescents (13-17 Years)
n=18 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54 mg) capsules
|
HLD200 in Children (6-12 Yrs)
n=11 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54mg) capsules
|
|---|---|---|
|
PK Parameters for Rate and Extent of Absorption of MPH: Tmax
|
17.1 hours
Standard Deviation 2.5
|
17.7 hours
Standard Deviation 2.5
|
PRIMARY outcome
Timeframe: 48hrsPopulation: All enrolled subjects included in analysis population.
Area under the methylphenidate plasma concentration-time curve to time point tz (AUC0-tz), where tz was the last time point over the time interval with a measurable drug concentration
Outcome measures
| Measure |
HLD200 in Adolescents (13-17 Years)
n=18 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54 mg) capsules
|
HLD200 in Children (6-12 Yrs)
n=11 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54mg) capsules
|
|---|---|---|
|
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-tz
|
105.5 ng.hr/mL
Standard Deviation 31.7
|
205.6 ng.hr/mL
Standard Deviation 80.4
|
PRIMARY outcome
Timeframe: 48hrsPopulation: All enrolled subjects included in analysis population.
The area under the methylphenidate plasma concentration-time curve to infinite time
Outcome measures
| Measure |
HLD200 in Adolescents (13-17 Years)
n=18 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54 mg) capsules
|
HLD200 in Children (6-12 Yrs)
n=11 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54mg) capsules
|
|---|---|---|
|
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-inf
|
109.6 ng.hr/mL
Standard Deviation 33.8
|
210.1 ng.hr/mL
Standard Deviation 80.9
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 48hrsPopulation: All enrolled subjects included in analysis population.
To determine the rate and extent of absorption of methylphenidate following a single treatment of HLD200 (B formulation; 54 mg) in children and adolescents with ADHD, plasma samples were collected at t=0, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, 36 and 48 hours post-HLD200 treatment and methylphenidate concentrations were determined.
Outcome measures
| Measure |
HLD200 in Adolescents (13-17 Years)
n=18 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54 mg) capsules
|
HLD200 in Children (6-12 Yrs)
n=11 Participants
Drug: HLD200 (methylphenidate hydrochloride; 54mg) capsules
|
|---|---|---|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=0 hrs
|
0.00 (ng/mL)
Standard Deviation 0.00
|
0.00 (ng/mL)
Standard Deviation 0.00
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=4 hrs
|
0.00 (ng/mL)
Standard Deviation 0.00
|
0.05 (ng/mL)
Standard Deviation 0.07
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=6 hrs
|
0.03 (ng/mL)
Standard Deviation 0.06
|
0.13 (ng/mL)
Standard Deviation 0.13
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=8 hrs
|
0.15 (ng/mL)
Standard Deviation 0.11
|
0.39 (ng/mL)
Standard Deviation 0.21
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=9 hrs
|
0.47 (ng/mL)
Standard Deviation 0.36
|
1.03 (ng/mL)
Standard Deviation 0.66
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=10 hrs
|
1.37 (ng/mL)
Standard Deviation 0.89
|
2.15 (ng/mL)
Standard Deviation 1.41
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=11 hrs
|
2.33 (ng/mL)
Standard Deviation 1.32
|
4.42 (ng/mL)
Standard Deviation 2.77
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=12 hrs
|
3.76 (ng/mL)
Standard Deviation 1.89
|
6.84 (ng/mL)
Standard Deviation 4.01
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t= 13 hrs
|
4.66 (ng/mL)
Standard Deviation 2.06
|
8.10 (ng/mL)
Standard Deviation 4.72
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=14 hrs
|
5.70 (ng/mL)
Standard Deviation 2.02
|
9.05 (ng/mL)
Standard Deviation 4.40
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=15 hrs
|
6.09 (ng/mL)
Standard Deviation 1.90
|
9.68 (ng/mL)
Standard Deviation 4.06
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=16 hrs
|
6.58 (ng/mL)
Standard Deviation 1.57
|
10.64 (ng/mL)
Standard Deviation 4.51
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=18 hrs
|
6.13 (ng/mL)
Standard Deviation 1.43
|
11.01 (ng/mL)
Standard Deviation 3.90
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=20 hrs
|
5.52 (ng/mL)
Standard Deviation 1.56
|
10.53 (ng/mL)
Standard Deviation 4.23
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=22 hrs
|
4.66 (ng/mL)
Standard Deviation 1.57
|
9.22 (ng/mL)
Standard Deviation 3.76
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=24 hrs
|
3.67 (ng/mL)
Standard Deviation 1.70
|
7.51 (ng/mL)
Standard Deviation 3.48
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=36 hrs
|
1.07 (ng/mL)
Standard Deviation 0.76
|
2.47 (ng/mL)
Standard Deviation 1.05
|
|
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
t=48 hrs
|
0.23 (ng/mL)
Standard Deviation 0.30
|
0.48 (ng/mL)
Standard Deviation 0.20
|
Adverse Events
Adolescents (13-17yrs)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Children (6-12 Yrs)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Adolescents (13-17yrs)
n=18 participants at risk
Drug: B-HLD200 54mg capsules (Methylphenidate Modified Release B Formulation) or Drug: C-HLD200 54mg capsules (Methylphenidate Modified Release C Formulation)
|
Children (6-12 Yrs)
n=11 participants at risk
Drug: B-HLD200 54mg capsules (Methylphenidate Modified Release B Formulation) or Drug: C-HLD200 54mg capsules (Methylphenidate Modified Release C Formulation)
|
|---|---|---|
|
Ear and labyrinth disorders
Cerumen Impaction
|
5.6%
1/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
11.1%
2/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
|
Gastrointestinal disorders
Flatulence
|
5.6%
1/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
|
Gastrointestinal disorders
Nausea
|
5.6%
1/18 • Baseline to 48 hours after the HLD200 dose
|
9.1%
1/11 • Baseline to 48 hours after the HLD200 dose
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
1/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/18 • Baseline to 48 hours after the HLD200 dose
|
18.2%
2/11 • Baseline to 48 hours after the HLD200 dose
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
11.1%
2/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
|
Infections and infestations
Musculoskeletal And Connective Tissue Disorders
|
5.6%
1/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
|
Infections and infestations
Myalgia
|
5.6%
1/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
|
Nervous system disorders
Dizziness
|
0.00%
0/18 • Baseline to 48 hours after the HLD200 dose
|
18.2%
2/11 • Baseline to 48 hours after the HLD200 dose
|
|
Nervous system disorders
Dizziness Postural
|
0.00%
0/18 • Baseline to 48 hours after the HLD200 dose
|
9.1%
1/11 • Baseline to 48 hours after the HLD200 dose
|
|
Nervous system disorders
Headache
|
5.6%
1/18 • Baseline to 48 hours after the HLD200 dose
|
0.00%
0/11 • Baseline to 48 hours after the HLD200 dose
|
Additional Information
Chief Scientific Officer
Ironshore Pharmaceuticals and Development, Inc.
Phone: 13457498174
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place