Clinical Trial Results:
Investigation of clinical comparability of semaglutide drug products based on the proposed and the approved drug substance manufacturing processes in participants with type 2 diabetes
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Summary
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EudraCT number |
2021-001501-69 |
Trial protocol |
SK |
Global end of trial date |
18 Sep 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Oct 2024
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First version publication date |
02 Oct 2024
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Other versions |
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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 |
NN9535-4820
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05478252 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Alle, Bagsvaerd, Denmark, 2880
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Public contact |
Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.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 |
14 Nov 2023
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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 |
18 Sep 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To establish clinical comparability between semaglutide J subcutaneous (s.c.) and semaglutide B s.c. on change from baseline in HbA1c at week 28 in subjects with T2D as add-on to stable dose of metformin.
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, last amended by the 64th World Medical Association General Assembly, October 2013, and International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice, including archiving of essential documents, E6(R2), Current step 4 version, 09 November 2016 and 21 CFR 312.120.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Aug 2022
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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 |
Canada: 30
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Country: Number of subjects enrolled |
Poland: 84
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Country: Number of subjects enrolled |
Slovakia: 65
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Country: Number of subjects enrolled |
United States: 135
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Country: Number of subjects enrolled |
South Africa: 74
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Worldwide total number of subjects |
388
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EEA total number of subjects |
149
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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) |
387
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial was conducted at 73 sites in Slovakia, Poland, South Africa, the United States and Canada. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects were randomised in a 3:1 manner to receive either semaglutide J or semaglutide B. | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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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, Carer | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Semaglutide J | ||||||||||||||||||||||||||||||
Arm description |
Subjects initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide J once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Semaglutide J, 1.34 mg/mL, 1.5 mL compact cartridge, PDS290
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.25, 0.5 or 1.0 mg once-weekly
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Arm title
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Semaglutide B | ||||||||||||||||||||||||||||||
Arm description |
Subjects initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide B once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Semaglutide B, 1.34 mg/mL, 1.5 mL compact cartridge, PDS290
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
0.25, 0.5 or 1.0 mg once-weekly
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Baseline characteristics reporting groups
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Reporting group title |
Semaglutide J
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Reporting group description |
Subjects initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide J once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Semaglutide B
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Reporting group description |
Subjects initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide B once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Semaglutide J
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Reporting group description |
Subjects initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide J once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||
Reporting group title |
Semaglutide B
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Reporting group description |
Subjects initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide B once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||
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End point title |
Change in glycosylated haemoglobin (HbA1c) | ||||||||||||
End point description |
Change in HbA1c from baseline (week 0) to end of treatment (week 28) is presented. The endpoint was evaluated based on the data from in-study period. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site. Full analysis set included all randomised subjects. Here, "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Primary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of treatment visit (visit 10; week 28)
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Statistical analysis description |
Full analysis set included all randomised participants. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
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Comparison groups |
Semaglutide J v Semaglutide B
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Number of subjects included in analysis |
376
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Analysis specification |
Post-hoc
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Analysis type |
non-inferiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-0.11
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.3 | ||||||||||||
upper limit |
0.08 | ||||||||||||
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End point title |
Number of Treatment Emergent Adverse Events (TEAEs) | ||||||||||||
End point description |
All presented adverse events are TEAE. A TEAE is defined as an adverse event with an onset date (or increase in severity) during the on-treatment observation period. On-treatment observation period is defined as from first drug date until the end of study. Safety analysis set included all subjects who are exposed to study intervention.
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End point type |
Secondary
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End point timeframe |
From the time of first dosing to end of study visit (visit 11; week 33)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change in body weight | ||||||||||||
End point description |
Change in body weight from baseline (week 0) to end of treatment (week 28) is presented. The endpoint was evaluated based on the data from in-study period. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site. Full analysis set included all randomised participants. Here, "Overall Number of Subjectss Analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of treatment visit (visit 10; week 28)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Occurrence of anti-semaglutide antibodies (yes/no) | |||||||||||||||
End point description |
Occurrence of anti-semaglutide antibodies for in-study observation period is presented. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site. In the reported data 'yes' infers who received anti sema antibodies, whereas 'No' infers who did not receive anti sema antibodies. Safety analysis set included all subjects who are exposed to study intervention. Here, "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of study visit (visit 11; week 33)
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Occurence of anti-semaglutide antibodies with in-vitro neutralising effect (Yes/no) | |||||||||
End point description |
Occurrence of anti-semaglutide antibodies with in-vitro neutralizing effect was to be performed based on positive cross -reactivity to GLP-1. Since there was no sample with positive cross -reactivity to GLP-1, no further analysis was performed for invitro neutralizing effect towards native-GLP1. Therefore, no data is available for this end point. In the reported data 'yes' infers who tested positive for anti-semaglutide antibodies whereas 'No' infers who tested negative for anti-semaglutide antibodies.
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End point type |
Secondary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of study visit (visit 11; week 33)
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| Notes [1] - In-vitro neutralizing effect was not performed on samples with GLP-1 positive cross reactivity. [2] - In-vitro neutralizing effect was not performed on samples with GLP-1 positive cross reactivity. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Occurence of in-vitro neutralising cross-reacting antibodies to endogenous GLP-1 (Yes/no) | |||||||||||||||
End point description |
Occurence of in-vitro neutralising cross-reacting antibodies to endogenous GLP-1 from baseline (week 0) to week 33 is presented. In the reported data 'yes' infers who tested positive for in-vitro neutralising cross-reacting antibodies to endogenous GLP-1 whereas 'No' infers who tested negative for in-vitro neutralizing cross-reacting antibodies to endogenous GLP-1. Safety analysis set included all subjects who are exposed to study intervention. Here, "Overall Number of Subjectts Analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of study visit (visit 11; week 33)
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| Notes [3] - There were no subjects available for analysis. |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Occurence of anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1) (Yes/no) | |||||||||||||||
End point description |
Occurrence of anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1) for in-study observation period is presented. The in-study period is defined as the uninterrupted time interval from date of randomisation to date of least contact with trial site. In the reported data 'yes' infers who tested positive for anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1) whereas 'No' infers who tested negative for anti-semaglutide binding antibodies cross-reacting with endogenous glucagon like peptide-1 (GLP-1). Safety analysis set included all subjects who are exposed to study intervention. Here, "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of study visit (visit 11; week 33)
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| Notes [4] - There were no subjects available for analysis. |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Anti-semaglutide antibodies level measured as percentage (%) Bound/Total | ||||||||||||
End point description |
Anti-semaglutide antibodies level measured as %Bound/Total from baseline (week 0) to week 33 is presented. Safety analysis set included all subjects who are exposed to study intervention. Here, "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of study visit (visit 11; week 33)
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| Notes [5] - There were no subjects available for analysis. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Anti-semaglutide antibodies level (measured as titre) | ||||||||||||
End point description |
Anti-semaglutide antibodies level measured as titre from baseline (week 0) to week 33 is presented. Safety analysis set included all subjects who are exposed to study intervention. Here, "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome measure.
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End point type |
Secondary
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End point timeframe |
From baseline visit (visit 2; week 0) to end of study visit (visit 11; week 33)
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| Notes [6] - There were no subjects available for analysis. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the time of first dosing (week 0) to end of study (week 33).
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Adverse event reporting additional description |
Treatment emergent adverse events presented, defined as adverse events with onset date (or increase in severity) during on-treatment observation period, defined as from 1st drug date until end of study. Safety analysis set: all participants who are exposed to study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26
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Reporting groups
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Reporting group title |
Semaglutide B
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Reporting group description |
Participants initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide B once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Semaglutide J
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Reporting group description |
Participants initially received 0.25 milligrams (mg) subcutaneous injections of semaglutide J once weekly and the dose was then escalated (0.25 mg in week 0 to week 4 and 0.5 mg in week 4 to week 8) once in 4 weeks until the target maintenance dose of 1.0 mg was reached which was maintained for a period of 20 weeks. Total treatment period was 28 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Jul 2022 |
This version of the protocol is prepared to include additional PK samples and analyses to allow PK comparability of semaglutide J s.c. and semaglutide B s.c., based on the Health Canada’s feedback.Population pharmacokinetics will be addressed in a modelling analysis plan and the totality of
evidence from all PK assessments will be presented as a collective whole in a comprehensive modelling report. Therefore, secondary PK objective has been removed from the protocol. |
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06 Dec 2022 |
This change has been made to increase the robustness and acceptability of the primary assessment and is based on recommendations from Health Authority. This is to maintain 80% power under the non-inferiority analysis that does not utilize historical data. This has been done to simplify and provide more clarity. This has been done to correct spelling
mistake.This has been removed as it is no longer defined in the protocol. |
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07 Jun 2023 |
This has been done to correct wrong specification. This has been done in accordance with feedback received from health authority. This has been done in accordance with the change of the estimands. This has been done to preserve the conservatism of the primary analysis and is aligned with feedback received from health authority. This has been done to correct the time range for sampling. This has been done to
maintain consistency between Section 4.3 and Section 6.1. This has been removed as it is no longer defined in protocol. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
