Trial Outcomes & Findings for Comparison of Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone (NCT NCT02777268)
NCT ID: NCT02777268
Last Updated: 2017-12-02
Results Overview
To compare the Cmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
-1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h
Results posted on
2017-12-02
Participant Flow
Recruitment Area: United Kingdom Location: Phase 1 Unit
Participant milestones
| Measure |
All Study Participants
5-way crossover study design involving Infacort and hydrocortisone at the following dose strengths:
Infacort 0.5mg Infacort 2mg Infacort 5mg Infacort 10mg Hydrocortisone 10mg
Each IMP was administered to each subject in a randomised, crossover manner over 5 treatment periods (1 treatment/period). During each treatment period, each subject was admitted to the Unit on the afternoon of Day 1 and remained in the Unit until completion of all scheduled assessments on Day 2. Each subject received their scheduled IMP on the morning of Day 2 at \~0700hrs (fasted). Each subject also received 1mg dexamethasone (to suppress endogenous cortisol production) at approximately 2200hrs on Day 1, and at approximately 0600hrs and 1200hrs on Day 2. All doses were administered with 200mL water. There were at least 7 days washout between each dose of IMP.
|
|---|---|
|
Overall Study
STARTED
|
16
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparison of Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone
Baseline characteristics by cohort
| Measure |
All Study Participants
n=16 Participants
5-way crossover study design involving Infacort and hydrocortisone at the following dose strengths:
Infacort 0.5mg Infacort 2mg Infacort 5mg Infacort 10mg Hydrocortisone 10mg
Each IMP was administered to each subject in a randomised, crossover manner over 5 treatment periods (1 treatment/period). During each treatment period, each subject was admitted to the Unit on the afternoon of Day 1 and remained in the Unit until completion of all scheduled assessments on Day 2. Each subject received their scheduled IMP on the morning of Day 2 at \~0700hrs (fasted). Each subject also received 1mg dexamethasone (to suppress endogenous cortisol production) at approximately 2200hrs on Day 1, and at approximately 0600hrs and 1200hrs on Day 2. All doses were administered with 200mL water. There were at least 7 days washout between each dose of IMP.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Age, Continuous
|
40.70 Years
STANDARD_DEVIATION 14.370 • n=93 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
United Kingdom
|
16 participants
n=93 Participants
|
|
Body Mass Index (BMI)
|
25.34 kg/m^2
STANDARD_DEVIATION 2.085 • n=93 Participants
|
|
Height (m)
|
1.773 Metres (m)
STANDARD_DEVIATION 0.081 • n=93 Participants
|
|
Weight (kg)
|
79.70 Kilograms (kg)
STANDARD_DEVIATION 8.543 • n=93 Participants
|
|
Medical History and Concurrent Conditions
|
0 Participants
n=93 Participants
|
|
Drug/Alcohol and HIV/Hepatitis Screening
|
0 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12hPopulation: Two subjects were excluded from the Infacort 10mg analysis population due to inadequate endogenous cortisol suppression prior to dosing.
To compare the Cmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg.
Outcome measures
| Measure |
Infacort 10mg
n=14 Participants
Multi-particulate granules from 10mg Infacort capsule
|
Hydrocortisone
n=14 Participants
1 (10 mg) tablet
Hydrocortisone: Tablet
|
Infacort 5mg
Multi-particulate granules from 1 (5mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10mg
Multi-particulate granules from 1 (10mg) capsule
Infacort: Multi-particulate granules
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Infacort vs Hydrocortisone
|
601.843 nmol/L
Geometric Coefficient of Variation 21.5
|
622.384 nmol/L
Geometric Coefficient of Variation 15.8
|
—
|
—
|
PRIMARY outcome
Timeframe: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12hPopulation: Two subjects were excluded from the Infacort 10mg analysis population due to inadequate endogenous cortisol suppression prior to dosing.
To compare the Tmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg.
Outcome measures
| Measure |
Infacort 10mg
n=14 Participants
Multi-particulate granules from 10mg Infacort capsule
|
Hydrocortisone
n=14 Participants
1 (10 mg) tablet
Hydrocortisone: Tablet
|
Infacort 5mg
Multi-particulate granules from 1 (5mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10mg
Multi-particulate granules from 1 (10mg) capsule
Infacort: Multi-particulate granules
|
|---|---|---|---|---|
|
Time to Reach the Maximum Plasma Concentration (Tmax) of Infacort vs Hydrocortisone
|
0.500 Hour
Standard Deviation 0.4031
|
1 Hour
Standard Deviation 0.4171
|
—
|
—
|
PRIMARY outcome
Timeframe: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12hPopulation: Two subjects were excluded from the Infacort 10mg analysis population due to inadequate endogenous cortisol suppression prior to dosing.
To compare the AUC0-t of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg. AUC0-t represents the total exposure to drug over time, hence the reporting of a single value below.
Outcome measures
| Measure |
Infacort 10mg
n=14 Participants
Multi-particulate granules from 10mg Infacort capsule
|
Hydrocortisone
n=14 Participants
1 (10 mg) tablet
Hydrocortisone: Tablet
|
Infacort 5mg
Multi-particulate granules from 1 (5mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10mg
Multi-particulate granules from 1 (10mg) capsule
Infacort: Multi-particulate granules
|
|---|---|---|---|---|
|
Area Under the Curve (AUC0-t) of Infacort vs Hydrocortisone
|
1836.718 hr*nmol/L
Geometric Coefficient of Variation 17.8
|
1803.278 hr*nmol/L
Geometric Coefficient of Variation 14.6
|
—
|
—
|
SECONDARY outcome
Timeframe: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12hTo determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg.
Outcome measures
| Measure |
Infacort 10mg
n=15 Participants
Multi-particulate granules from 10mg Infacort capsule
|
Hydrocortisone
n=15 Participants
1 (10 mg) tablet
Hydrocortisone: Tablet
|
Infacort 5mg
n=15 Participants
Multi-particulate granules from 1 (5mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10mg
n=14 Participants
Multi-particulate granules from 1 (10mg) capsule
Infacort: Multi-particulate granules
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg
|
92.220 nmol/L
Geometric Coefficient of Variation 22.9
|
242.798 nmol/L
Geometric Coefficient of Variation 16.0
|
424.310 nmol/L
Geometric Coefficient of Variation 14.8
|
601.843 nmol/L
Geometric Coefficient of Variation 21.5
|
SECONDARY outcome
Timeframe: -1h, -0.5h, 0h, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12hTo determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg.
Outcome measures
| Measure |
Infacort 10mg
n=15 Participants
Multi-particulate granules from 10mg Infacort capsule
|
Hydrocortisone
n=15 Participants
1 (10 mg) tablet
Hydrocortisone: Tablet
|
Infacort 5mg
n=15 Participants
Multi-particulate granules from 1 (5mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10mg
n=14 Participants
Multi-particulate granules from 1 (10mg) capsule
Infacort: Multi-particulate granules
|
|---|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg
|
0.500 Hours
Standard Deviation 0.2236
|
0.500 Hours
Standard Deviation 0.3010
|
0.500 Hours
Standard Deviation 0.3162
|
0.500 Hours
Standard Deviation 0.4031
|
SECONDARY outcome
Timeframe: 1 dayTo determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg.
Outcome measures
| Measure |
Infacort 10mg
n=14 Participants
Multi-particulate granules from 10mg Infacort capsule
|
Hydrocortisone
n=14 Participants
1 (10 mg) tablet
Hydrocortisone: Tablet
|
Infacort 5mg
n=14 Participants
Multi-particulate granules from 1 (5mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10mg
n=14 Participants
Multi-particulate granules from 1 (10mg) capsule
Infacort: Multi-particulate granules
|
|---|---|---|---|---|
|
Area Under the Curve (AUC0-t) of Infacort at Doses of 0.5, 2, 5 and 10 mg
|
326.129 H*nmol/L
Geometric Coefficient of Variation 21.3
|
648.407 H*nmol/L
Geometric Coefficient of Variation 16.6
|
1127.579 H*nmol/L
Geometric Coefficient of Variation 15.2
|
1836.718 H*nmol/L
Geometric Coefficient of Variation 17.8
|
SECONDARY outcome
Timeframe: 1 dayTo assess the safety and tolerability of Infacort® throughout the study. For a full list of TEAEs per arm, please refer to the Adverse Events section.
Outcome measures
| Measure |
Infacort 10mg
n=16 Participants
Multi-particulate granules from 10mg Infacort capsule
|
Hydrocortisone
1 (10 mg) tablet
Hydrocortisone: Tablet
|
Infacort 5mg
Multi-particulate granules from 1 (5mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10mg
Multi-particulate granules from 1 (10mg) capsule
Infacort: Multi-particulate granules
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Assessed by Medical Dictionary for Regulatory Activities (MedDRA) Dictionary, Version 16.0.
|
7 TEAEs
|
—
|
—
|
—
|
Adverse Events
Infacort 0.5 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Infacort 2 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Infacort 5 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Infacort 10 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Hydrocortisone
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Infacort 0.5 mg
n=16 participants at risk
Multi-particulate granules from 1 (0.5 mg) capsule
Infacort: Multi-particulate granules
|
Infacort 2 mg
n=16 participants at risk
Multi-particulate granules from 1 (2 mg) capsule
Infacort: Multi-particulate granules
|
Infacort 5 mg
n=16 participants at risk
Multi-particulate granules from 1 (5 mg) capsule
Infacort: Multi-particulate granules
|
Infacort 10 mg
n=16 participants at risk
Multi-particulate granules from 1 (10 mg) capsule
Infacort: Multi-particulate granules
|
Hydrocortisone
n=16 participants at risk
1 (10 mg) tablet
Hydrocortisone: Tablet
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16 • Number of events 1 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
6.2%
1/16 • Number of events 1 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
6.2%
1/16 • Number of events 1 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
12.5%
2/16 • Number of events 2 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
|
Vascular disorders
Flushing
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
6.2%
1/16 • Number of events 1 • From study start (19 July 2013) to completion (9 September 2013)
|
|
Nervous system disorders
Headache
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
6.2%
1/16 • Number of events 1 • From study start (19 July 2013) to completion (9 September 2013)
|
0.00%
0/16 • From study start (19 July 2013) to completion (9 September 2013)
|
Additional Information
Dr Girish Sharma
Simbec Research Limited
Phone: +44 1443 690977
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator must obtain written consent from the Sponsor prior to any publication of results.
- Publication restrictions are in place
Restriction type: OTHER