Dexlansoprazole in Asian Participants With Gastroesophageal Reflux Disease

A Phase 4, Open-Label Study in Patients From Asia With Gastroesophageal Reflux Disease Treated With Dexlansoprazole

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02351960

Enrollment

296

Registered

2015-01-30

Start date

2015-03-19

Completion date

2016-07-13

Last updated

2017-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastroesophageal Reflux Disease

Keywords

Drug therapy, GERD, Dexlansoprazole

Brief summary

The purpose of this study is to evaluate the effectiveness of symptom control in gastroesophageal reflux disease (GERD) participants following treatment with dexlansoprazole.

Detailed description

The drug being tested in this study is called dexlansoprazole. A dual delayed release formulation of dexlansoprazole, referred to as dexlansoprazole modified release (dexlansoprazole MR) was tested to treat people who have gastroesophageal reflux disease (GERD). This study looked at the healing of the esophageal lining of the GERD participants who took dexlansoprazole MR. The study enrolled 296 patients. Participants were assigned to two study groups based on the endoscopy screening procedures to receive treatments as follows: * Dexlansoprazole 30 mg to participants with non-erosive reflux disease (NERD) * Dexlansoprazole 60 mg to participants with erosive esophagitis (EE) All participants were asked to take one capsule in the morning each day throughout the study. All participants were asked to record the presence and maximum severity of daytime and nighttime heartburn and regurgitation symptoms during screening and, if assigned to a treatment group, throughout the duration of the study using the supplied paper diary. This multi-center trial was conducted in Asia (Hong Kong, Taiwan, South Korea). The overall time to participate in this study was up to 8 weeks. Participants would make up to 3 visits to the clinic, and would be contacted by telephone 30 days after the last dose of study drug for a follow-up assessment.

Interventions

DRUGDexlansoprazole

Dexlansoprazole capsules

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

- 1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements 2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any procedures 3. Has persistent typical gastroesophageal reflux disease (GERD) symptoms (heartburn and/or acid regurgitation) for at least 6 months and a frequency of GERD symptoms is at least 4 days within the past 7 days prior to the screening visit 4. Meets one of the following diagnoses verified by the screening endoscopy 1. Has macroscopically normal esophageal mucosa on endoscopy and may thereby be eligible for assignment to the nonerosive reflux disease (NERD) study group 2. Has evidence of erosive esophageal reflux disease on endoscopy, Los Angeles (LA) classification grades B-D, and thereby may be eligible for assignment to the erosive esophagitis (EE) study group 5. Is able and willing to record GERD symptoms in a subject diary and has completed the diary at least for 7 consecutive days during the screening period 6. Male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose 7. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study 8. All female participants of childbearing potential must have a negative urine pregnancy test at Screening and a negative urine pregnancy test at Day -1. Participants who have had a bilateral tubal ligation, hysterectomy or are post-menopausal (the absence of menses for 1-2 years with a Follicle-Stimulating Hormone \[FSH\] level \>40 IU/L or absence of menses for \>2 years) are not required to use birth control

Exclusion criteria

1. Has received any investigational compound within 30 days prior to Screening 2. Known hypersensitivity to any proton pump inhibitor (including lansoprazole, omeprazole, rabeprazole, pantoprazole or esomeprazole), any component of dexlansoprazole 3. Use of a H2 blocker or a PPI other than dexlansoprazole during screening and throughout the study. Previous use of Dexlansoprazole before screening 4. Endoscopic Barrett's esophagus and/or definite dysplastic changes in the esophagus 5. Active gastric or duodenal ulcers within 4 weeks of the first dose of study drug 6. History of dilatation of esophageal strictures, other than a Schatzki's ring (a ring of mucosal tissue near the lower esophageal sphincter) 7. Co-existing diseases affecting the esophagus, (eg, esophageal varices, scleroderma, viral, fungal infection or esophageal stricture), history of radiation therapy or cryotherapy to the esophagus, caustic or physiochemical trauma such as sclerotherapy to the esophagus 8. Chronic use (\>12 doses/month) of non-;steroidal anti-inflammatory drugs (NSAIDs) including COX 2 NSAIDs within 30 days prior to screening period and throughout the study, however, low dose aspirin up to 325 mg per day is allowed 9. In the judgment of the investigator, participant has clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening 10. Has a history or clinical manifestations of significant organ failure which would preclude their successful completion of the study 11. Participants using drugs with significant anticholinergic effects such as tricyclics who cannot stay on a stable dose for 4 weeks prior to dosing and throughout the study 12. Participants with known biliary disease 13. Participants with the need for continuous anticoagulant therapy 14. Participants with cancer (except basal cell and squamous cell carcinoma of the skin) within 3 years prior to Screening 15. Any condition that may require inpatient surgery during the course of the study 16. Has abnormal laboratory values that suggest a clinically significant underlying disease or condition that may prevent the subject from entering the study; or subject with the following lab abnormalities: Creatinine \>1.5 mg/dL, Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) \>2.0X the upper limits of normal, or Total Bilirubin \>2.0 mg/dL with AST/ALT elevated above normal values 17. Known to have acquired immunodeficiency syndrome (AIDS) 18. Current or historical evidence of Zollinger-Ellison syndrome or other hypersecretory condition 19. History of gastric, duodenal or esophageal surgery except simple oversew of an ulcer 20. Acute upper gastrointestinal (UGI) hemorrhage within 4 weeks of endoscopy 22\. Has received blood products within 3 months prior to the first dose of study drug 23. History of alcohol abuse \[\>21 units (1 unit = 12 oz beer, 1.5 oz hard liquor, or 5 oz wine) per week\] or illegal drug use or drug addiction in the 12 months prior to Screening 24. Participants who, in the opinion of the investigator, are unable to comply with the requirements of the study or are unsuitable for any reason 25. is required to take excluded medications 26. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period 27. If male, the participant intends to donate sperm during the course of this study or for 30 days thereafter

Design outcomes

Primary

Measure	Time frame	Description
Percentage of 24-Hour Heartburn and Acid Regurgitation-Free Days in Non-Erosive Reflux Disease (NERD) Participants	Up to Week 4	NERD participants were asked to keep a paper diary of daily heartburn and acid regurgitation-free days and the percentage of heartburn and acid regurgitation-free days was recorded.
Percentage of 24-Hour Heartburn and Acid Regurgitation-Free Days in Erosive Esophagitis (EE) Participants	Up to Week 8	EE participants were asked to keep a paper diary of daily heartburn and acid regurgitation-free days and the percentage of heartburn and acid regurgitation-free days was calculated.

Secondary

Measure	Time frame	Description
Percentage of Nights (Participant Sleep Time) Without Nighttime Heartburn and Acid Regurgitation	Up to 4 weeks for NERD participants and up to 8 weeks for EE participants	Participants were asked to keep a daily paper diary. The percentage of nights without nighttime heartburn and acid regurgitation in both the group was assessed by participant dairy entries.
Percentage of Nights (Participant Sleep Time) Without Nighttime Heartburn	Up to 4 weeks for NERD participants and up to 8 weeks for EE participants	Participants were asked to keep a daily paper diary. The percentage of nights without nighttime heartburn in both the group was assessed by participant diary entries.
Percentage of 24-hour Heartburn-free Days	Up to 4 weeks for NERD participants and up to 8 weeks for EE participants	Participants were asked to keep a daily paper diary. The percentage of 24-hour heartburn free days following study drug treatments was assessed by the participant diary entries.
Number of Participants With Severity of Gastroesophageal Reflux Disease (GERD) Symptoms	Up to 4 weeks for NERD participants and up to 8 weeks for EE participants	The severity of participants' GERD symptoms based on the investigator's assessment among all participants was evaluated at Week 4 or Week 8. GERD symptoms were assessed on a 5-point scale, wherein 1=no symptom, 2=mild, 3=moderate, 4=severe and 5=very severe. GERD symptoms include heartburn (HB), acid regurgitation (AR), dysphagia (dysp), belching (bch) and epigastric pain (EP).
Percentage of Participants in the EE Group Who Had Endoscopically Evaluated Macroscopic Healing of Their Esophagus	Week 8	Participants underwent endoscopy to determine the percentage of participants with macroscopic healing of their esophagus showing at least 1 Los Angeles (LA) grade classification grade improvement at week 8. Endoscopic findings classified according to the Los Angeles classification: Grade Normal - endoscopy reveals no mucosal break Grade A- one or more mucosal breaks \<5 mm in maximal length Grade B - one or more mucosal breaks \>5 mm, but without continuity across mucosal folds Grade C - Mucosal breaks continuous between \>2 mucosal folds, but involving less than 75% of the esophageal circumference Grade D - Mucosal breaks involving more than 75% of the esophageal circumference.
Percentage of Nights (Participant Sleep Time) Without Nighttime Acid Regurgitation	Up to 4 weeks for NERD participants and up to 8 weeks for EE participants	Participants were asked to keep a daily paper diary. The percentage of nights without nighttime acid regurgitation in both the group was assessed by participant diary entries.
Percentage of 24-hour Acid Regurgitation-free Days	Up to 4 weeks for NERD participants and up to 8 weeks for EE participants	Participants were asked to keep a daily paper diary. The percentage of 24-hour acid regurgitation-free days following study drug treatments was assessed by participant's diary entries.

Countries

Hong Kong, South Korea, Taiwan

Participant flow

Recruitment details

Participants took part in the study at 12 investigative sites in Hong Kong, South Korea, Taiwan from 19 March 2015 to 13 July 2016.

Pre-assignment details

Participants with a diagnosis of non-erosive reflux disease (NERD) were enrolled to receive dexlansoprazole 30 mg and participants with erosive esophagitis (EE) were enrolled to receive dexlansoprazole 60 mg.

Participants by arm

Arm	Count
Dexlansoprazole 30 mg Dexlansoprazole 30 mg, capsules, orally, once daily for up to 4 weeks to participants with non-erosive reflux disease (NERD).	208
Dexlansoprazole 60 mg Dexlansoprazole 60 mg, capsules orally, once daily for up to 8 weeks to participants with erosive esophagitis (EE).	88
Total	296

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Pretreatment Event/Adverse Event	6	3
Overall Study	Significant Protocol Deviation	0	5
Overall Study	Voluntary Withdrawal	5	4

Baseline characteristics

Characteristic	Dexlansoprazole 30 mg	Dexlansoprazole 60 mg	Total
12-Lead Electrocardiogram (ECG) Abnormal but not Clinically Significant	67 participants	33 participants	100 participants
12-Lead Electrocardiogram (ECG) Within Normal Limits	141 participants	55 participants	196 participants
Age, Continuous	53.6 years STANDARD_DEVIATION 13.62	51.7 years STANDARD_DEVIATION 12.51	52.6 years STANDARD_DEVIATION 13.06
Age, Customized 45-<65 years	102 participants	42 participants	144 participants
Age, Customized <45 years	60 participants	29 participants	89 participants
Age, Customized ≥65 years	46 participants	17 participants	63 participants
BMI categories 25-<30 kg/m^2	43 participants	33 participants	76 participants
BMI categories <25 kg/m^2	158 participants	46 participants	204 participants
BMI categories ≥30 kg/m^2	7 participants	9 participants	16 participants
Body Mass Index	23.00 kg/m^2 STANDARD_DEVIATION 3.305	25.11 kg/m^2 STANDARD_DEVIATION 4.16	24.05 kg/m^2 STANDARD_DEVIATION 3.732
Height	161.5 cm STANDARD_DEVIATION 8.43	165.0 cm STANDARD_DEVIATION 9.65	163.25 cm STANDARD_DEVIATION 9.04
Race/Ethnicity, Customized Asian	208 participants	87 participants	295 participants
Race/Ethnicity, Customized Multiracial	0 participants	1 participants	1 participants
Region of Enrollment Hong Kong	13 participants	6 participants	19 participants
Region of Enrollment Korea, Republic Of	195 participants	12 participants	207 participants
Region of Enrollment Taiwan, Province Of China	0 participants	70 participants	70 participants
Sex: Female, Male Female	72 Participants	49 Participants	121 Participants
Sex: Female, Male Male	136 Participants	39 Participants	175 Participants
Smoking History Current Smoker	15 participants	11 participants	26 participants
Smoking History Ex-smoker	24 participants	16 participants	40 participants
Smoking History Never Smoked	169 participants	61 participants	230 participants
Weight	60.26 kg STANDARD_DEVIATION 11.619	68.84 kg STANDARD_DEVIATION 14.986	64.55 kg STANDARD_DEVIATION 13.302

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	7 / 208	2 / 88
serious Total, serious adverse events	0 / 208	2 / 88

Outcome results

Primary

Percentage of 24-Hour Heartburn and Acid Regurgitation-Free Days in Erosive Esophagitis (EE) Participants

EE participants were asked to keep a paper diary of daily heartburn and acid regurgitation-free days and the percentage of heartburn and acid regurgitation-free days was calculated.

Time frame: Up to Week 8

Population: FAS included all participants who received at least 1 dose of study drug and had post-baseline data for the appropriate efficacy variable. Here number of participants analyzed are the participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Dexlansoprazole 30 mg	Percentage of 24-Hour Heartburn and Acid Regurgitation-Free Days in Erosive Esophagitis (EE) Participants	65.45 percentage of days

Primary

Percentage of 24-Hour Heartburn and Acid Regurgitation-Free Days in Non-Erosive Reflux Disease (NERD) Participants

NERD participants were asked to keep a paper diary of daily heartburn and acid regurgitation-free days and the percentage of heartburn and acid regurgitation-free days was recorded.

Time frame: Up to Week 4

Population: Full analysis set (FAS) included all participants who received at least 1 dose of study drug and had post-baseline data for the appropriate efficacy variable.

Arm	Measure	Value (MEDIAN)
Dexlansoprazole 30 mg	Percentage of 24-Hour Heartburn and Acid Regurgitation-Free Days in Non-Erosive Reflux Disease (NERD) Participants	26.92 percentage of days

Secondary

Number of Participants With Severity of Gastroesophageal Reflux Disease (GERD) Symptoms

The severity of participants' GERD symptoms based on the investigator's assessment among all participants was evaluated at Week 4 or Week 8. GERD symptoms were assessed on a 5-point scale, wherein 1=no symptom, 2=mild, 3=moderate, 4=severe and 5=very severe. GERD symptoms include heartburn (HB), acid regurgitation (AR), dysphagia (dysp), belching (bch) and epigastric pain (EP).