Clinical Trial Results:
A placebo-controlled, double-blind (sponsor open), randomised, crossover study to assess the efficacy, safety, and tolerability of GSK2798745 in participants with chronic cough
Summary
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EudraCT number |
2017-002265-21 |
Trial protocol |
GB |
Global end of trial date |
08 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Sep 2019
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First version publication date |
22 Sep 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
207702
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Mar 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Oct 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To compare the efficacy of 7 days dosing of GSK2798745 with placebo in participants with idiopathic or treatment-resistant chronic cough.
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Protection of trial subjects |
Not Applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Apr 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 17
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Worldwide total number of subjects |
17
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EEA total number of subjects |
17
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
10
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Study was conducted at 4 centers in the United Kingdom. Participants who met eligibility criteria entered a 2-period crossover study. Participants were randomized to either placebo or GSK2798745 in each Treatment Period (each 7 days, with a 14-21 day washout). Total duration of participation was 10.5 weeks. Study terminated on grounds of futility | |||||||||||||||
Pre-assignment
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Screening details |
A total of 34 participants were screened of which 17 failed screening and 17 participants were included in the study. | |||||||||||||||
Period 1
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Period 1 title |
Treatment Period 1 (Up to 7 days)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo/GSK2798745 | |||||||||||||||
Arm description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of placebo on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Investigational medicinal product name |
2.4 mg GSK2798745
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of 2.4 mg GSK2798748 on Day 1 and one tablet on Days 2 to 7, via the oral
route with a glass of water.
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Arm title
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GSK2798745/Placebo | |||||||||||||||
Arm description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
2.4 mg GSK2798745
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of 2.4 mg GSK2798748 on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of placebo on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Period 2
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Period 2 title |
Wash-out period (14-21 days)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo/GSK2798745 | |||||||||||||||
Arm description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of placebo on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Investigational medicinal product name |
2.4 mg GSK2798745
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of 2.4 mg
GSK2798748 on Day 1 and one tablet on Days 2 to 7, via the oral
route with a glass of water.
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Arm title
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GSK2798745/Placebo | |||||||||||||||
Arm description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of placebo on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Investigational medicinal product name |
2.4 mg GSK2798745
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of 2.4 mg GSK2798748 on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Period 3
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Period 3 title |
Treatment Period 2 (Up to 7 days)
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo/GSK2798745 | |||||||||||||||
Arm description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of placebo on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Investigational medicinal product name |
2.4 mg GSK2798745
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of 2.4 mg
GSK2798748 on Day 1 and one tablet on Days 2 to 7, via the oral
route with a glass of water.
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Arm title
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GSK2798745/Placebo | |||||||||||||||
Arm description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
2.4 mg GSK2798745
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of 2.4 mg GSK2798748 on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
||||||||||||||||
Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants were randomized to receive two tablets of placebo on Day 1 and one tablet on Days 2 to 7, via the oral route with a glass of water.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo/GSK2798745
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Reporting group description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GSK2798745/Placebo
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Reporting group description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
All study participants
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants who were randomized to either of the two treatment sequences Placebo/GSK2798745 and GSK2798745/Placebo and received GSK2798745 and placebo in either Treatment period 1 or 2 were included. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
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Subject analysis set title |
Placebo
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
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Subject analysis set title |
GSK2798745
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
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End points reporting groups
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Reporting group title |
Placebo/GSK2798745
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Reporting group description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||
Reporting group title |
GSK2798745/Placebo
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Reporting group description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||
Reporting group title |
Placebo/GSK2798745
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Reporting group description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||
Reporting group title |
GSK2798745/Placebo
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Reporting group description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||
Reporting group title |
Placebo/GSK2798745
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Reporting group description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||
Reporting group title |
GSK2798745/Placebo
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Reporting group description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||
Subject analysis set title |
All study participants
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All participants who were randomized to either of the two treatment sequences Placebo/GSK2798745 and GSK2798745/Placebo and received GSK2798745 and placebo in either Treatment period 1 or 2 were included. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
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Subject analysis set title |
Placebo
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
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Subject analysis set title |
GSK2798745
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
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End point title |
Total cough counts during day time hours following 7-days of dosing | ||||||||||||
End point description |
Coughs were monitored using the VitaloJAK cough monitor. Total cough counts during day-time (10 hours) was calculated from the time of monitor being attached i.e. immediately after dosing on Day 7 to 10 hours past the time of monitoring. Total cough counts were log-transformed prior to analysis. A non-informative prior was used. Analysis was performed using a Bayesian mixed model adjusting for subject-level and period-adjusted baselines, treatment and period. Subject-level baseline is defined as the mean of two period-specific baselines. Period-adjusted baseline is defined as difference between the period-specific baseline and subject-level baseline for each period. Posterior median and 95% credible interval is reported. All Subjects Population included all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to treatment they actually received. Only those participants with data available at specified data points were analyzed.
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End point type |
Primary
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End point timeframe |
Up to 10 hours post-dose on Day 7 of each treatment period
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
Placebo v GSK2798745
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Number of subjects included in analysis |
32
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
Method |
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Parameter type |
Ratio | ||||||||||||
Point estimate |
1.336
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Confidence interval |
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level |
90% | ||||||||||||
sides |
2-sided
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lower limit |
0.965 | ||||||||||||
upper limit |
1.847 | ||||||||||||
Notes [1] - Treatment comparison ratio of GSK2798745 and placebo using posterior median ratio and 90% credible interval is presented. |
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End point title |
Number of participants reporting adverse events (AEs) and serious adverse events (SAEs) | |||||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to 45 days
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Change from Baseline values for clinical chemistry parameters: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate amino transferase (AST) and creatinine kinase (CK) | ||||||||||||||||||||||||
End point description |
Blood samples were collected for the analysis of clinical chemistry parameters including ALP, ALT, AST and CK. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 of each treatment period
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Change from Baseline values for clinical chemistry parameter: direct bilirubin, total bilirubin and creatinine | |||||||||||||||||||||
End point description |
Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, total bilirubin and creatinine. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 for each treatment period
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Change from Baseline values for clinical chemistry parameters: calcium, glucose, potassium, sodium and urea | |||||||||||||||||||||||||||
End point description |
Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium, sodium and urea/blood urea nitrogen (BUN). Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 of each treatment period
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline values for clinical chemistry parameter: Total protein | ||||||||||||
End point description |
Blood samples were collected for the analysis of clinical chemistry parameter total protein. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 of each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of participants with abnormal values of cardiac troponin | |||||||||
End point description |
Cardiac troponin values was measured in participants.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to 45 days
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline values for hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and white blood cell (WBC) count | |||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and WBC count. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 of each treatment period
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline values for hematology parameter: hemoglobin | ||||||||||||
End point description |
Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 for each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline values for hematology parameter: hematocrit | ||||||||||||
End point description |
Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 of each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline values for hematology parameter: Mean corpuscular hemoglobin (MCH) | ||||||||||||
End point description |
Blood samples were collected for the analysis of hematology parameter: MCH. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 for each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline values for hematology parameter: Mean corpuscular volume (MCV) | ||||||||||||
End point description |
Blood samples were collected for the analysis of hematology parameter: MCV. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 of each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline values for hematology parameter: Red blood cell (RBC) count | ||||||||||||
End point description |
Blood samples were collected for the analysis of hematology parameter: RBC count. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 for each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline values for hematology parameter: reticulocytes | ||||||||||||
End point description |
Blood samples were collected for the analysis of hematology parameter: reticulocytes. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (Day -1) and Day 8 for each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of participants with abnormal urinalysis data | ||||||||||||
End point description |
Urine samples were collected for analysis of urinalysis data by dipstick method. Number of participants with abnormal urinalysis data has been presented. Abnormality was defined as value of potential clinical importance (PCI). PCI was flagged when a result changed from negative on Day 1 (pre-dose) to positive on Day 8. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Day 8
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in diastolic blood pressure (DBP) and systolic blood pressure (SBP) | ||||||||||||||||||
End point description |
Blood pressure was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline (pre-dose on Day 1) and Day 8 of each treatment period
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline in temperature | ||||||||||||
End point description |
Temperature was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (pre-dose on Day 1) and Day 8 of each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline in heart rate | ||||||||||||
End point description |
Heart rate was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline (pre-dose on Day 1) and Day 8 of each treatment period
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Number of participants with abnormal electrocardiogram (ECG) findings | |||||||||||||||||||||
End point description |
Twelve-lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with abnormal-clinically significant and abnormal-not clinically significant values has been presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category title).
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline (pre-dose on Day 1) and Day 8 of each treatment period
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
AEs and SAEs were collected from the start of the treatment up to 45 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
AEs and SAEs were collected for All Subjects population
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GSK2798745
|
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Reporting group description |
Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
09 Oct 2017 |
Amendment No.01: The primary reason for amending the protocol was the removal of the Simplified Nutritional Appetite Questionnaire (SNAQ). |
||
22 Nov 2017 |
Amendment No.02: Medicines and Healthcare Products Regulatory Agency (MHRA) requested:
• Addition of the Columbia Suicidality Severity Rating Scale (CSSRS) at Follow-up.
• That in case of an emergency, the investigator has the sole responsibility for determining if unblinding of a participant’s treatment assignment is warranted.
• Addition of adverse event stopping criteria. |
||
25 Jun 2018 |
Amendment No.03: A non-substantial protocol amendment was made to clarify the inclusion criteria and make administrative corrections. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |