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Pharmacokinetic and Safety of Dexlansoprazole in Adolescents With Gastroesophageal Reflux Disease

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ClinicalTrials.gov Identifier: NCT00847210
Recruitment Status : Completed
First Posted : February 19, 2009
Results First Posted : October 5, 2010
Last Update Posted : February 2, 2012
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastroesophageal Reflux
Intervention Drug: Dexlansoprazole MR
Enrollment 36
Recruitment Details Participants were enrolled at 3 investigative sites in the United States from 31 May 2009 to 10 September 2009.
Pre-assignment Details Participants were enrolled in one of two, dexlansoprazole modified release (MR), once-daily (QD) treatment groups. 100% of participants randomized completed this study.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Period Title: Overall Study
Started 18 18
Completed 18 18
Not Completed 0 0
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD Total
Hide Arm/Group Description Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days. Total of all reporting groups
Overall Number of Baseline Participants 18 18 36
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 18 participants 36 participants
14.6  (1.65) 14.6  (1.89) 14.6  (1.75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 18 participants 36 participants
Female
11
  61.1%
11
  61.1%
22
  61.1%
Male
7
  38.9%
7
  38.9%
14
  38.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants 18 participants 36 participants
18 18 36
1.Primary Outcome
Title Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) Pharmacokinetic Parameter
Hide Description Tmax: Time to reach the Maximum Plasma Concentration (Cmax), equal to time (hours) to Cmax, as observed on Day 7.
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had Tmax estimated were included in the analysis for this parameter. One participant in the 30 mg group was excluded from the pharmacokinetic (PK) analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. There was no imputation for missing values.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 17 18
Mean (Standard Deviation)
Unit of Measure: hours
4.65  (2.909) 3.31  (1.519)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 30 mg QD, Dexlansoprazole MR 60 mg QD
Comments This study was not powered for any hypothesis testing. For Tmax, an analysis of variance (ANOVA) model was fitted that included fixed effect of age group, regimen and interaction of age group and regimen. If the interaction term was not statistically significant, it was not included in the final model. The site effect was also tested in the model, and was not included in the final model if it was not statistically significant (P>0.05). Pairwise comparisons between regimens were conducted.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.095
Comments There was no statistical significant difference (p-value >0.05) in Tmax between the 30 mg and 60 mg dose group. Both age group and site did not have statistically significant effects on Tmax.
Method ANOVA
Comments [Not Specified]
2.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration Pharmacokinetic Parameter.
Hide Description Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had Cmax estimated were included in the analysis for this parameter. One participant in the 30 mg group was excluded from the PK analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. There was no imputation for missing values.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 17 18
Mean (Standard Deviation)
Unit of Measure: ng/mL
691  (367.5) 1136  (582.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 30 mg QD, Dexlansoprazole MR 60 mg QD
Comments This study was not powered for any hypothesis testing. For natural logarithm of dose-normalized Cmax, an ANOVA model was fitted that included fixed effect of age group, regimen and interaction of age group and regimen. If the interaction term was not statistically significant, it was not included in the final model. Site effect was tested in the model, and was not included in the final model if not statistically significant (P>0.05). Pairwise comparisons between regimens were conducted.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.289
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter ratio of the central values for Cmax
Estimated Value 1.210
Confidence Interval (2-Sided) 90%
0.897 to 1.630
Estimation Comments Ninety percent confidence intervals for assessing the dose proportionality of dexlansoprazole pharmacokinetics between regimens were computed based on the frame work of ANOVA.
3.Primary Outcome
Title AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration Pharmacokinetic Parameter.
Hide Description Area Under the Plasma Concentration Versus Time Curve (AUC(0-tlqc)) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had AUC(0-tlqc) estimated were included in the analysis for this parameter. One participant in the 30 mg group was excluded from the PK analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. There was no imputation for missing values.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 17 18
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL/mg
2842.32  (1313.827) 5113.72  (2987.508)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 30 mg QD, Dexlansoprazole MR 60 mg QD
Comments This study was not powered for any hypothesis testing. For Tmax, an ANOVA model was fitted that included fixed effect of age group (12-14 years and 15 17 years), regimen and interaction of age group and regimen. If the interaction term was not statistically significant, it was not included in the final model. The site effect was also tested in the model, and was not included in the final model if it was not statistically significant (P>0.05). Pairwise comparisons between regimens were conducted.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.402
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the dose-normalized AUC(0-tlqc)
Estimated Value 1.158
Confidence Interval (2-Sided) 90%
0.864 to 1.551
Estimation Comments Ninety percent confidence intervals for assessing the dose proportionality of dexlansoprazole AUC(0-tlqc) between regimens were computed based on the frame work of ANOVA.
4.Primary Outcome
Title AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose Pharmacokinetic Parameter.
Hide Description AUC(0-24) is measure of Area Under the Curve over the dosing interval (tau) (AUC(0-tau]), where tau is the length of the dosing interval - 24 hours in this study).
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had AUC(0-24) estimated were included in the analysis for this parameter. One participant in the 30 mg group was excluded from the PK analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. There was no imputation for missing values.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 16 18
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL/mg
2886.26  (1355.182) 5119.81  (2986.453)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dexlansoprazole MR 30 mg QD, Dexlansoprazole MR 60 mg QD
Comments This study was not powered for any hypothesis testing. For Tmax, an ANOVA model was fitted that included fixed effect of age group (12-14 years and 15 17 years), regimen and interaction of age group and regimen. If the interaction term was not statistically significant, it was not included in the final model. The site effect was also tested in the model, and was not included in the final model if it was not statistically significant (P>0.05). Pairwise comparisons between regimens were conducted.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.388
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of the central values for dose-nor
Estimated Value 1.168
Confidence Interval (2-Sided) 90%
0.864 to 1.579
Estimation Comments Ninety percent confidence intervals for assessing the dose proportionality of dexlansoprazole AUC(0-24) between regimens were computed based on the frame work of ANOVA.
5.Primary Outcome
Title Terminal Phase Elimination Half-life (T1/2) Pharmacokinetic Parameter.
Hide Description Terminal Phase Elimination Half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had T1/2 estimated were included in the analysis for this parameter. One participant in the 30 mg group was excluded from the PK analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. No statistical tests were performed.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 16 18
Mean (Standard Deviation)
Unit of Measure: hours
1.66  (0.871) 2.59  (1.379)
6.Primary Outcome
Title Oral Clearance (CL/F) Pharmacokinetic Parameter.
Hide Description CL/F is apparent clearance of the drug from the plasma, calculated as the drug dose divided AUC(0-24), expressed in L/hr.
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had CL/F estimated were included in the analysis. One participant in the 30 mg group was excluded from the PK analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. There was no imputation for missing values. No statistical tests were performed.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 16 18
Mean (Standard Deviation)
Unit of Measure: liter/hr
12.81  (6.092) 15.29  (7.524)
7.Primary Outcome
Title Terminal Elimination Rate Constant (λz) Pharmacokinetic Parameter.
Hide Description Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body.
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had λz estimated were included in the analysis. One participant in the 30 mg group was excluded from the PK analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. There was no imputation for missing values. No statistical tests were performed.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 16 18
Mean (Standard Deviation)
Unit of Measure: 1/hr
0.5264  (0.25425) 0.3404  (0.17406)
8.Primary Outcome
Title Apparent Volume of Distribution (Vz/F) Pharmacokinetic Parameter.
Hide Description Vz/F is the distribution of a drug between plasma and the rest of the body following oral administration, calculated as CL/F divided by λz.
Time Frame After 7 days of dosing.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who had Vz/F estimated were included in the analysis for this parameter. One participant in the 30 mg group was excluded from the PK analysis because most of the PK samples were not collected, and hence no PK parameters were estimable. There was no imputation for missing values. No statistical tests were performed.
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description:
Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days.
Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
Overall Number of Participants Analyzed 16 18
Mean (Standard Deviation)
Unit of Measure: L
28.90  (21.208) 58.50  (46.100)
Time Frame Treatment-emergent adverse events are defined as those reported after the first dose and no more than 30 days after the last dose of study drug.
Adverse Event Reporting Description There were no deaths, serious adverse events or significant adverse events during the study.
 
Arm/Group Title Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Hide Arm/Group Description Dexlansoprazole MR 30 mg, capsules, orally, once daily for up to 7 days. Dexlansoprazole MR 60 mg, capsules, orally, once daily for up to 7 days.
All-Cause Mortality
Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/18 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dexlansoprazole MR 30 mg QD Dexlansoprazole MR 60 mg QD
Affected / at Risk (%) Affected / at Risk (%)
Total   7/18 (38.89%)   5/18 (27.78%) 
Gastrointestinal disorders     
Dyspepsia  1  0/18 (0.00%)  1/18 (5.56%) 
Eructation  1  0/18 (0.00%)  1/18 (5.56%) 
Abdominal Pain  1  4/18 (22.22%)  0/18 (0.00%) 
Vomiting  1  0/18 (0.00%)  2/18 (11.11%) 
General disorders     
Feelings of Body Temperature Change  1  0/18 (0.00%)  1/18 (5.56%) 
Injury, poisoning and procedural complications     
Contusion  1  0/18 (0.00%)  1/18 (5.56%) 
Nervous system disorders     
Headache  1  1/18 (5.56%)  2/18 (11.11%) 
Dizziness  1  1/18 (5.56%)  1/18 (5.56%) 
Presyncope  1  1/18 (5.56%)  1/18 (5.56%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/18 (5.56%)  0/18 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
For outcome measures #4, 5, 6, 7 and 8, outcomes could not be estimated for one participant in the 30 mg dose group.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights therefrom or any data, information or materials obtained or generated in the performance of it’s obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda’s sole discretion.
Results Point of Contact
Name/Title: Sr. VP Clinical Science
Organization: Takeda Global Research and Development Center, Inc.
Phone: 800-778-2860
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00847210     History of Changes
Other Study ID Numbers: T-P107-163
U1111-1114-1891 ( Registry Identifier: WHO )
First Submitted: February 18, 2009
First Posted: February 19, 2009
Results First Submitted: September 8, 2010
Results First Posted: October 5, 2010
Last Update Posted: February 2, 2012