GSK1325756 Relative Bioavailability Study in Healthy Elderly Subjects

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT03457727

Collaborator

(none)

Enrollment

Location

Arms

4.6

Actual Duration (Months)

8.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This 2-part study will be carried out on healthy elderly subjects to evaluate relative bioavailability of danirixin formulations. Part A will support the selection of the formulation and Part B will assess food effect, bioavailability and pharmacokinetic (PK) profile of selected formulation from Part A. Danirixin is currently administered with food, therefore the investigation of food effect for the selected formulation could potentially enable dosing without food. Approximately 16 subjects will be included in Part A and approximately 24 subjects will be included in Part B. Both parts will include a screening phase, treatment phase with in-between washout period and a follow-up phase.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Danirixin Drug: Omeprazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Subjects will receive danirixin reference and test formulations in a cross-over manner.Subjects will receive danirixin reference and test formulations in a cross-over manner.

Masking:

None (Open Label)

Masking Description:

This will be an open-label study and blinding will not be performed.

Primary Purpose:

Treatment

Official Title:

A Two Part, Randomized, Open-label, Cross Over Study in Healthy Elderly Participants to Evaluate the Relative Bioavailability of Hydrobromide Salt Tablet Formulations of Danirixin in the Fed and Fasted States, and to Evaluate the Effect of Food and Gastric Acid Secretion Suppression on Danirixin Pharmacokinetics Following Administration of Hydrobromide Salt Tablets

Actual Study Start Date :

Mar 7, 2018

Actual Primary Completion Date :

Jul 25, 2018

Actual Study Completion Date :

Jul 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects receiving danirixin: Part A Subjects will receive a single oral dose of 50 mg danirixin reference and test formulations with food and 240 mL of water in a cross-over manner.	Drug: Danirixin Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.
Experimental: Subjects receiving danirixin without omeprazole: Part B Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) in fasted or fed state in a cross-over manner.	Drug: Danirixin Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.
Experimental: Subjects receiving danirixin with omeprazole: Part B Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) along with once daily 40 mg OMP capsule in fasted or fed state in a cross-over manner.	Drug: Danirixin Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner. Drug: Omeprazole Omeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects.

Arm

Intervention/Treatment

Experimental: Subjects receiving danirixin: Part A

Subjects will receive a single oral dose of 50 mg danirixin reference and test formulations with food and 240 mL of water in a cross-over manner.

Drug: Danirixin

Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.

Experimental: Subjects receiving danirixin without omeprazole: Part B

Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) in fasted or fed state in a cross-over manner.

Drug: Danirixin

Experimental: Subjects receiving danirixin with omeprazole: Part B

Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) along with once daily 40 mg OMP capsule in fasted or fed state in a cross-over manner.

Drug: Danirixin

Drug: Omeprazole

Omeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects.

Outcome Measures

Primary Outcome Measures

Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the pharmacokinetic (PK) profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Maximum Observed Concentration (Cmax) of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Number of Participants With Any Adverse Event (AE) and Serious Adverse Events (SAEs) in Part 1 [Up to 29 days in Part 1]
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Number of Participants With Vital Signs of Potential Clinical Concern in Part 1 [Up to 29 days in Part 1]
Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.
Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 1 [Up to 29 days in Part 1]
Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 1 are presented.
Number of Participants With Laboratory Values of Potential Clinical Concern in Part 1 [Up to 29 days in Part 1]
Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct bilirubin, creatinine, sodium alanine, aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.

Secondary Outcome Measures

Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC [0-24]) of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time to Occurrence of Cmax (Tmax) of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Terminal Half-life (t1/2) of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of Danirixin for Part 1 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Maximum Observed Concentration (Cmax) of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time to Maximum Observed Concentration (Tmax) of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Terminal Half-life (t1/2) of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Lag Time Before Observable Concentration (Tlag) of Danirixin for Part 2 [Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2]
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 2 [Up to 52 days in Part 2]
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Number of Participants With Vital Signs of Potential Clinical Concern in Part 2 [Up to 52 days in Part 2]
Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.
Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 2 [Up to 52 days in Part 2]
Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 2 are presented.
Number of Participants With Laboratory Values of Potential Clinical Concern in Part 2 [Up to 52 days in Part 2]
Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate, Aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct, bilirubin, creatinine sodium alanine, Aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subjects must be 65 to 80 years of age inclusive, at the Screening Visit.
Subjects who are healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring or a subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives. Additionally, laboratory assessments that are specifically listed in the inclusion or exclusion criteria and are outside of the reference range can be repeated once during the screening period.
Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 34 kg per meter square (kg/m^2) (inclusive).
Male or female subjects will be included. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 60 hours after the last dose of study treatment.
Capable of giving signed informed consent.
AST, ALT, alkaline phosphatase and bilirubin <= 1.5 × upper limit of normal (ULN) (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).
Resting BP of <= 160/90 millimeters of mercury (mmHg), irrespective of anti-hypertensive medication status for the subject.
Able to consume the Food and Drug Administration (FDA) defined high fat meal within 30 minutes in each of the four treatment periods where study treatment is administered in a fed state.

Exclusion Criteria:

Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test [TST; defined as a skin induration <5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history] or a positive (not indeterminate) QuantiFERON®-TB Gold test.
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
ALT >1.5x ULN
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Corrected QT interval (QTc) >450 milliseconds (msec).
Use of prescription or non-prescription drugs, including proton pump inhibitors, histamine receptor 2 antagonists, systemic antacid medications (unless these can be held during the study), vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment until completion of the last study assessment , unless in the opinion of the investigator and GSK Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety. Some examples of exceptions (permitted medications) are: Stable dose of anti-hypertensive medication for at least 3 months prior to the screening visit; Stable dose of lipid-lowering medications (statins or fibrates) for at least 3 months prior to the screening visit; Antacids up to 24 hours prior to dosing.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Participation in a previous clinical trial with danirixin within 1 year prior to the first dosing day in the current study.
Female Subjects: Positive urine beta-human chorionic gonadotropin (beta-hCG) test at screening.
Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
For potent immunosuppressive agents, presence of the Hepatitis B core antibody (HBcAb) should also lead to exclusion from the study even if HBsAg is negative.
Positive pre-study drug/alcohol screen.
Positive human immunodeficiency virus (HIV) antibody test.
Regular use of known drugs of abuse.
Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study treatment until collection of the final blood sample.
Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 90 days prior to screening.
Sensitivity to heparin or heparin-induced thrombocytopenia.
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Overland Park	Kansas	United States	66211

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03457727

Other Study ID Numbers:

207573

First Posted:

Mar 7, 2018

Last Update Posted:

May 19, 2021

Last Verified:

Apr 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by GlaxoSmithKline

Danirixin

Healthy

Food effect

Relative Bioavailability

Hydrobromide Salt

Additional relevant MeSH terms:

Pulmonary Disease, Chronic Obstructive

Omeprazole

Study Results

Participant Flow

Recruitment Details	This two-part study assessed the relative bioavailability of Danirixin (DNX) tablet formulations along with effect of food and gastric acid secretion suppression on DNX pharmacokinetics. This study was conducted at a single center in the United States from 07-Mar-2018 to 25-Jul-2018.
Pre-assignment Detail	Danirixin hemihydrate salt tablet formulation manufactured using roller compaction (RC) was compared to test formulations manufactured by direct compression (DC) with an excipient hydroxypropyl methylcellulose (HPMC) to evaluate the most appropriate formulation/dosing regimen. A total of 40 participants were enrolled in the study.

Arm/Group Title	DNX 50 mg 600RC/475DC/600DC/600DC-5% HPMC in Fed State	DNX 50mg 600RC/475DC/600DC/600DC-5% HPMC in Fasted State	DNX 50 mg 475 DC Under Fasted/Normal/Fat Meal/ Mono-fat Meal	DNX 50 mg 475 DC+OMP 40mg Under Fasted/Normal/Fat Meal State
Arm/Group Description	Participants received a sequence of the following: single oral dose of 50 milligrams (mg) DNX hydrobromide (HBr) hemihydrate tablet formulation (600 mg tablet manufactured by RC [600 RC]) on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (475 mg tablet manufactured by DC [475 DC]) on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (600 DC) on Day 1 of treatment period 3 and 50 mg DNX HBr hemihydrate 600 DC tablet formulation with containing 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fed state (with a high fat meal). The treatment periods were separated by a washout period of 5 days.	Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 600 RC on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC on Day 1 of treatment period 2, a single oral dose 50 mg DNX HBr hemihydrate 600 DC on Day 1 of treatment period 3 and a single oral dose of 50 mg DNX HBr hemihydrate 600 DC with 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fasted state. The treatment periods were separated by a washout period of 5 days.	Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC tablet formulation in fasted state on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with normal meal on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with high fat meal in treatment period 3, followed by a single oral dose of 50 mg DNX HBr monohydrate 475 DC with high fat meal in treatment period 4. The treatment periods were separated by a washout period of 5 days.	Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC in fasted state along with 40 mg omeprazole (OMP) during treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with normal meal in treatment period 2 and a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with high fat meal in treatment period 3. The treatment periods were separated by a washout period of 5 days. OMP was administered from Day -4 of each treatment period through washout periods.
Period Title: Part 1, Period 1 (1 Day)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	0	0	12	12
COMPLETED	0	0	12	12
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	0	0	12	12
COMPLETED	0	0	12	11
NOT COMPLETED	0	0	0	1
Period Title: Part 1, Period 1 (1 Day)
STARTED	0	0	12	11
COMPLETED	0	0	12	11
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	0	0	12	11
COMPLETED	0	0	12	11
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	0	0	12	11
COMPLETED	0	0	12	11
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	0	0	12	11
COMPLETED	0	0	12	11
NOT COMPLETED	0	0	0	0
Period Title: Part 1, Period 1 (1 Day)
STARTED	0	0	12	0
COMPLETED	0	0	12	0
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	DNX 50 mg 600RC/475DC/600DC/600DC-5% HPMC in Fed State	DNX 50mg 600RC/475DC/600DC/600DC-5% HPMC in Fasted State	DNX 50 mg 475 DC Under Fasted/Normal/Fat Meal/ Mono-fat Meal	DNX 50 mg 475 DC+OMP 40mg Under Fasted/Normal/Fat Meal State	Total
Arm/Group Description	Participants received a sequence of the following: single oral dose of 50 milligrams (mg) DNX hydrobromide (HBr) hemihydrate tablet formulation (600 mg tablet manufactured by RC [600 RC]) on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (475 mg tablet manufactured by DC [475 DC]) on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (600 DC) on Day 1 of treatment period 3 and 50 mg DNX HBr hemihydrate 600 DC tablet formulation with containing 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fed state (with a high fat meal). The treatment periods were separated by a washout period of 5 days.	Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 600 RC on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC on Day 1 of treatment period 2, a single oral dose 50 mg DNX HBr hemihydrate 600 DC on Day 1 of treatment period 3 and a single oral dose of 50 mg DNX HBr hemihydrate 600 DC with 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fasted state. The treatment periods were separated by a washout period of 5 days.	Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC tablet formulation in fasted state on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with normal meal on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with high fat meal in treatment period 3, followed by a single oral dose of 50 mg DNX HBr monohydrate 475 DC with high fat meal in treatment period 4. The treatment periods were separated by a washout period of 5 days.	Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC in fasted state along with 40 mg omeprazole (OMP) during treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with normal meal in treatment period 2 and a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with high fat meal in treatment period 3. The treatment periods were separated by a washout period of 5 days. OMP was administered from Day -4 of each treatment period through washout periods.	Total of all reporting groups
Overall Participants	8	8	12	12	40
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	69.4 (3.54)	70.9 (4.58)	71.3 (4.14)	69.4 (2.68)	70.3 (3.70)
Sex: Female, Male (Count of Participants)
Female	4 50%	6 75%	4 33.3%	8 66.7%	22 55%
Male	4 50%	2 25%	8 66.7%	4 33.3%	18 45%
Race/Ethnicity, Customized (Count of Participants) [Number]
Black or African American	1 12.5%	0 0%	0 0%	2 16.7%	3 7.5%
White	7 87.5%	8 100%	12 100%	10 83.3%	37 92.5%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the pharmacokinetic (PK) profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK Population includes all participants for whom a PK sample was obtained and analyzed. Only those participants with data available at specified time frame were analyzed.

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	5	7	7	6	6	7	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms per milliliter]	6166.7 (19.20)	6052.9 (14.18)	5816.4 (22.99)	5996.1 (26.31)	11394.6 (30.07)	11285.7 (32.72)	10957.4 (31.55)	11230.8 (28.21)

2. Primary Outcome

Title	Maximum Observed Concentration (Cmax) of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time frame were analyzed

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	7	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Nanograms/milliliter]	761.5 (27.22)	712.8 (20.53)	762.3 (37.23)	659.2 (47.40)	2708.2 (26.22)	2418.5 (27.78)	2607.1 (30.24)	2511.8 (24.19)

3. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Serious Adverse Events (SAEs) in Part 1
Description	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Time Frame	Up to 29 days in Part 1

Outcome Measure Data

Analysis Population Description
Modified Intent-to-treat (mITT) Population includes all randomized participants

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	8	8	8	8
Any AE	1 12.5%	0 0%	0 0%	0 0%	2 5%	1 NaN	1 NaN	1 NaN
Any SAE	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN

4. Primary Outcome

Title	Number of Participants With Vital Signs of Potential Clinical Concern in Part 1
Description	Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.
Time Frame	Up to 29 days in Part 1

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	8	8	8	8
Count of Participants [Participants]	2 25%	2 25%	2 16.7%	2 16.7%	0 0%	0 NaN	0 NaN	0 NaN

5. Primary Outcome

Title	Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 1
Description	Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 1 are presented.
Time Frame	Up to 29 days in Part 1

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	8	8	8	8
Count of Participants [Participants]	1 12.5%	2 25%	2 16.7%	2 16.7%	2 5%	1 NaN	2 NaN	1 NaN

6. Primary Outcome

Title	Number of Participants With Laboratory Values of Potential Clinical Concern in Part 1
Description	Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct bilirubin, creatinine, sodium alanine, aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.
Time Frame	Up to 29 days in Part 1

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	8	8	8	8
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	1 NaN	0 NaN

7. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	7	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	5515.9 (24.54)	5573.6 (17.65)	5524.7 (22.15)	5287.0 (28.27)	11480.1 (28.07)	10977.2 (30.52)	10636.5 (32.09)	11015.8 (28.35)

8. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC [0-24]) of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	7	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	4919.5 (27.19)	4952.0 (18.25)	4984.8 (24.27)	4705.2 (27.96)	10744.8 (26.07)	10419.9 (27.78)	10029.3 (32.19)	10319.9 (26.14)

9. Secondary Outcome

Title	Time to Occurrence of Cmax (Tmax) of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	7	8	8	8
Mean (Standard Deviation) [Hours]	3.897 (0.9894)	3.653 (0.5089)	3.585 (1.2942)	4.158 (1.3556)	1.165 (0.3794)	1.331 (0.7536)	1.214 (0.2669)	1.342 (0.3768)

10. Secondary Outcome

Title	Terminal Half-life (t1/2) of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	5	7	7	6	6	7	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours]	9.638 (17.60)	10.904 (19.33)	8.916 (29.74)	9.888 (26.18)	8.298 (36.18)	9.498 (26.76)	9.391 (45.40)	9.107 (29.56)

11. Secondary Outcome

Title	Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	7	8	8	8
Mean (Standard Deviation) [Hours]	47.660 (0.2178)	47.587 (0.2200)	44.657 (8.3551)	44.757 (8.3813)	44.372 (8.9730)	41.789 (10.9667)	41.699 (10.9179)	44.531 (8.3335)

12. Secondary Outcome

Title	Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of Danirixin for Part 1
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	600RC High Fat	475DC High Fat	600DC High Fat	600DC 5%HPMC High Fat	600RC Fasted	475DC Fasted	600DC Fasted	600DC 5%HPMC Fasted
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition
Measure Participants	8	8	8	8	7	8	8	8
Mean (Standard Deviation) [Hours]	0.323 (0.3812)	0.383 (0.5917)	0.383 (0.5918)	0.511 (0.6661)	0.000 (0.000)	0.065 (0.1830)	0.000 (0.0000)	0.000 (0.0000)

13. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	10	12	11	9	10	7
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	12426.4 (35.85)	7761.2 (41.31)	8136.7 (32.85)	7356.4 (34.65)	14615.2 (24.23)	10185.0 (34.57)	8782.5 (45.73)

14. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	11	12	12	11	11	11
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	12026.9 (37.00)	7484.2 (39.37)	7757.2 (31.77)	6986.9 (32.54)	12903.9 (37.02)	9023.8 (42.46)	7885.4 (46.30)

15. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	11	12	12	10	10	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms/milliliter]	11096.7 (36.64)	6482.2 (37.93)	6706.6 (28.49)	6187.1 (30.41)	12762.9 (23.58)	8681.0 (32.68)	7590.8 (37.96)

16. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	11	12	12	11	11	11
Geometric Mean (Geometric Coefficient of Variation) [Nanograms/milliliter]	2317.4 (44.90)	989.9 (47.91)	969.9 (37.80)	1019.8 (38.90)	2292.5 (43.18)	1389.7 (43.59)	1132.5 (35.26)

17. Secondary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	11	12	12	11	11	11
Geometric Mean (Geometric Coefficient of Variation) [Hours]	1.271 (0.3374)	3.749 (0.6458)	4.150 (1.5008)	3.355 (1.3724)	1.978 (0.8770)	2.887 (0.7802)	3.752 (1.7384)

18. Secondary Outcome

Title	Terminal Half-life (t1/2) of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	10	12	11	9	10	7
Geometric Mean (Geometric Coefficient of Variation) [Hours]	10.647 (26.80)	11.424 (21.51)	11.484 (11.21)	11.652 (20.01)	11.304 (15.02)	10.913 (24.37)	8.975 (33.78)

19. Secondary Outcome

Title	Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	11	12	12	11	11	11
Geometric Mean (Geometric Coefficient of Variation) [Hours]	45.139 (6.6767)	47.144 (0.4440)	47.200 (0.4262)	46.741 (0.4843)	45.217 (7.0764)	45.242 (7.0723)	40.869 (10.8896)

20. Secondary Outcome

Title	Lag Time Before Observable Concentration (Tlag) of Danirixin for Part 2
Description	Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Time Frame	Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2

Outcome Measure Data

Analysis Population Description
PK population. Only those participants with data available at specified time points were analyzed

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	11	12	12	11	11	11
Geometric Mean (Geometric Coefficient of Variation) [Hours]	0.000 (0.0000)	0.283 (0.3554)	0.641 (0.4405)	0.386 (0.4922)	0.000 (0.0000)	0.423 (0.3097)	0.370 (0.6461)

21. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 2
Description	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Time Frame	Up to 52 days in Part 2

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	12	12	12	11	11	12
Any AE	1 12.5%	1 12.5%	1 8.3%	0 0%	0 0%	0 NaN	3 NaN
Any SAE	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	0 NaN

22. Secondary Outcome

Title	Number of Participants With Vital Signs of Potential Clinical Concern in Part 2
Description	Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.
Time Frame	Up to 52 days in Part 2

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	12	12	12	11	11	12
Count of Participants [Participants]	2 25%	3 37.5%	4 33.3%	4 33.3%	4 10%	3 NaN	4 NaN

23. Secondary Outcome

Title	Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 2
Description	Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 2 are presented.
Time Frame	Up to 52 days in Part 2

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	12	12	12	11	11	12
Count of Participants [Participants]	1 12.5%	2 25%	1 8.3%	3 25%	1 2.5%	2 NaN	2 NaN

24. Secondary Outcome

Title	Number of Participants With Laboratory Values of Potential Clinical Concern in Part 2
Description	Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate, Aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct, bilirubin, creatinine sodium alanine, Aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.
Time Frame	Up to 52 days in Part 2

Outcome Measure Data

Analysis Population Description
mITT Population

Arm/Group Title	475DC-Fasted	475DC-Normal Meal	475DC-High Fat	475DC-MONO High Fat	475DC Fasted OMP	475DC Normal Meal OMP	475DC High Fat OMP
Arm/Group Description	Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal	Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal	Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
Measure Participants	12	12	12	12	11	11	12
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	1 NaN

Adverse Events

	600RC High Fat		475DC High Fat		600DC High Fat		600DC 5%HPMC High Fat		600RC Fasted		475DC Fasted		600DC Fasted		600DC 5%HPMC Fasted		475DC-Fasted		475DC-Normal Meal		475DC-High Fat		475DC-MONO High Fat		475DC-Fasted OMP		475DC-Normal Meal OMP		475DC-High Fat OMP
Time Frame	On-Treatment serious adverse events (SAEs) and non-serious AEs (nSAEs) were collected from start of study treatment until 81 days
Adverse Event Reporting Description	On-Treatment SAEs and nSAEs were reported for mITT Population.

Arm/Group Title	600RC High Fat		475DC High Fat		600DC High Fat		600DC 5%HPMC High Fat		600RC Fasted		475DC Fasted		600DC Fasted		600DC 5%HPMC Fasted		475DC-Fasted		475DC-Normal Meal		475DC-High Fat		475DC-MONO High Fat		475DC-Fasted OMP		475DC-Normal Meal OMP		475DC-High Fat OMP
Arm/Group Description	Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal		Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal		Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal		Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal		Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition		Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition		Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition		Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition		Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state		Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal		Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal		Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal		Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition		Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal		Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/11 (0%)		0/11 (0%)		0/12 (0%)
Serious Adverse Events
	600RC High Fat		475DC High Fat		600DC High Fat		600DC 5%HPMC High Fat		600RC Fasted		475DC Fasted		600DC Fasted		600DC 5%HPMC Fasted		475DC-Fasted		475DC-Normal Meal		475DC-High Fat		475DC-MONO High Fat		475DC-Fasted OMP		475DC-Normal Meal OMP		475DC-High Fat OMP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/11 (0%)		0/11 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	600RC High Fat		475DC High Fat		600DC High Fat		600DC 5%HPMC High Fat		600RC Fasted		475DC Fasted		600DC Fasted		600DC 5%HPMC Fasted		475DC-Fasted		475DC-Normal Meal		475DC-High Fat		475DC-MONO High Fat		475DC-Fasted OMP		475DC-Normal Meal OMP		475DC-High Fat OMP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		2/8 (25%)		1/8 (12.5%)		1/8 (12.5%)		1/8 (12.5%)		1/12 (8.3%)		1/12 (8.3%)		1/12 (8.3%)		0/12 (0%)		0/11 (0%)		0/11 (0%)		3/12 (25%)
Gastrointestinal disorders
Diarrhoea	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	1/8 (12.5%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2
Abnormal faeces	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Nausea	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Vomiting	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Dyspepsia	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2
General disorders
Vessel puncture site haematoma	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Bursitis	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Musculoskeletal chest pain	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Nervous system disorders
Headache	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Somnolence	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email	GSKClinicalSupportHD@gsk.com

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03457727

Other Study ID Numbers:

207573

First Posted:

Mar 7, 2018

Last Update Posted:

May 19, 2021

Last Verified:

Apr 1, 2021

GSK1325756 Relative Bioavailability Study in Healthy Elderly Subjects

Study Details

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Adverse Events

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