Trial Outcomes & Findings for Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects (NCT NCT01860703)
NCT ID: NCT01860703
Last Updated: 2014-11-12
Results Overview
Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
50 participants
Primary outcome timeframe
24-hour interval
Results posted on
2014-11-12
Participant Flow
First subject enrolled: 17 November 2012 Last subject completed: 19 December 2012 The study was carried out at Celerion, a research facility used for conducting clinical trials.
Participant milestones
| Measure |
ABCD
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment A = single oral dose of 33 mg/kg deferiprone Treatment B = single oral dose of 50 mg/kg deferiprone Treatment C = single oral dose of placebo Treatment D = single oral dose of moxifloxacin
|
BDAC
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment B = single oral dose of 50 mg/kg deferiprone Treatment D = single oral dose of moxifloxacin Treatment A = single oral dose of 33 mg/kg deferiprone Treatment C = single oral dose of placebo
|
CADB
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment C = single oral dose of placebo Treatment A = single oral dose of 33 mg/kg deferiprone Treatment D = single oral dose of moxifloxacin Treatment B = single oral dose of 50 mg/kg deferiprone
|
DCBA
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment D = single oral dose of moxifloxacin Treatment C = single oral dose of placebo Treatment B = single oral dose of 50 mg/kg deferiprone Treatment A = single oral dose of 33 mg/kg deferiprone
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
13
|
13
|
12
|
12
|
|
Overall Study
COMPLETED
|
11
|
8
|
11
|
10
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
1
|
2
|
Reasons for withdrawal
| Measure |
ABCD
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment A = single oral dose of 33 mg/kg deferiprone Treatment B = single oral dose of 50 mg/kg deferiprone Treatment C = single oral dose of placebo Treatment D = single oral dose of moxifloxacin
|
BDAC
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment B = single oral dose of 50 mg/kg deferiprone Treatment D = single oral dose of moxifloxacin Treatment A = single oral dose of 33 mg/kg deferiprone Treatment C = single oral dose of placebo
|
CADB
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment C = single oral dose of placebo Treatment A = single oral dose of 33 mg/kg deferiprone Treatment D = single oral dose of moxifloxacin Treatment B = single oral dose of 50 mg/kg deferiprone
|
DCBA
All subjects received the same 4 treatments, separated by at least 7 days of washout, but were randomized to receive them in different orders. Subjects in this arm received them in the following order:
Treatment D = single oral dose of moxifloxacin Treatment C = single oral dose of placebo Treatment B = single oral dose of 50 mg/kg deferiprone Treatment A = single oral dose of 33 mg/kg deferiprone
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
4
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Overall Study
Personal reason
|
1
|
0
|
1
|
0
|
Baseline Characteristics
Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects
Baseline characteristics by cohort
| Measure |
All Subjects
n=50 Participants
Subjects in this cross-over study all received one dose of each the following: A) a maximum therapeutic dose of 33 mg deferiprone, B) a supratherapeutic dose of 50 mg/kg deferiprone, C) placebo, and D) moxifloxacin (active control). They were randomized to receive these products in different orders: ABCD, BDAC, CADB, or DCBA. Treatments were separated by a 7-day washout period.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
50 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
46 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
49 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: Cardiodynamic Analysis Set : all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement).
Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=45 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone
|
1.4 milliseconds
Standard Deviation 4.92
|
-1.6 milliseconds
Standard Deviation 4.72
|
—
|
—
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: Cardiodynamic Analysis Set : all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement).
Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=48 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=45 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 50 mg/kg Deferiprone
|
3.5 milliseconds
Standard Deviation 5.28
|
-1.7 milliseconds
Standard Deviation 6.36
|
—
|
—
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The Cardiodynamic Analysis Set consisted of all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement).
The maximum post-dose QT/QTc interval for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=48 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
n=45 Participants
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
n=46 Participants
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Maximum Postdose QT/QTc Interval
QTcF ≤ 450 msec
|
100 percentage of participants
|
96 percentage of participants
|
98 percentage of participants
|
89 percentage of participants
|
|
Maximum Postdose QT/QTc Interval
QTcF > 450 to ≤ 480 msec
|
0 percentage of participants
|
4 percentage of participants
|
2 percentage of participants
|
11 percentage of participants
|
|
Maximum Postdose QT/QTc Interval
QTcF > 480 to ≤ 500 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
|
Maximum Postdose QT/QTc Interval
QTcF > 500 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
PRIMARY outcome
Timeframe: 24-hour intervalPopulation: The Cardiodynamic Analysis Set consisted of all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement).
Maximum Change From Baseline (dQT/dQTc) for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=48 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
n=45 Participants
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
n=46 Participants
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Maximum Change From Baseline (dQT/dQTc)
QTcF ≤ 30 msec
|
100 percentage of participants
|
100 percentage of participants
|
100 percentage of participants
|
96 percentage of participants
|
|
Maximum Change From Baseline (dQT/dQTc)
QTcF >30 but ≤ 60 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
4 percentage of participants
|
|
Maximum Change From Baseline (dQT/dQTc)
QTcF >60 msec
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From administration of the first dose until 7 days +/- 1 day following the final dosePopulation: The Safety Analysis Set consisted of all subjects who received at least 1 dose of study medication and had at least 1 safety assessment.
Number of participants with adverse events following therapeutic and supratherapeutic doses of deferiprone
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=48 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
n=45 Participants
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
n=46 Participants
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events
|
12 participants
|
35 participants
|
10 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 24-hour intervalPopulation: The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected.
To evaluate the Cmax of deferiprone and deferiprone 3-O-glucuronide following administration of single doses of 33 and 50 mg/kg deferiprone in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=48 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Cmax of Deferiprone and Deferiprone 3-O Glucuronide
Cmax of serum deferiprone
|
34.1 μg/mL
Standard Deviation 8.9
|
54.4 μg/mL
Standard Deviation 16.4
|
—
|
—
|
|
Cmax of Deferiprone and Deferiprone 3-O Glucuronide
Cmax of serum deferiprone 3-O-glucuronide
|
35.2 μg/mL
Standard Deviation 8.5
|
51.4 μg/mL
Standard Deviation 13.4
|
—
|
—
|
SECONDARY outcome
Timeframe: 24-hour intervalPopulation: The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected.
To evaluate the Tmax of deferiprone and deferiprone 3-O-glucuronide following administration of single doses of 33 and 50 mg/kg deferiprone in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=48 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Tmax of Deferiprone and Deferiprone 3-O-glucuronide
Tmax of serum deferiprone
|
0.8185 hour
Full Range 0.6 • Interval 0.321 to 2.13
|
0.8175 hour
Full Range 0.9 • Interval 0.567 to 4.07
|
—
|
—
|
|
Tmax of Deferiprone and Deferiprone 3-O-glucuronide
Tmax of serum deferiprone -O-glucuronide
|
3.066 hour
Full Range 0.7 • Interval 1.39 to 4.07
|
3.071 hour
Full Range 0.7 • Interval 2.07 to 6.07
|
—
|
—
|
SECONDARY outcome
Timeframe: 24-hour intervalPopulation: The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected.
AUC0-infinity was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=48 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC0-infinity for serum deferiprone
|
95.4 μg *hr/mL
Standard Deviation 18.03
|
152.1 μg *hr/mL
Standard Deviation 22.2
|
—
|
—
|
|
AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide
AUC0-infinity for serum deferiprone -O-glucuronide
|
205.5 μg *hr/mL
Standard Deviation 42.8
|
331.2 μg *hr/mL
Standard Deviation 74.7
|
—
|
—
|
SECONDARY outcome
Timeframe: 24-hour intervalPopulation: The PK population consisted of all subjects who had taken study medication and had at least 1 PK sample collected.
T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers. Serial blood samples were collected prior to dosing and within 5 minutes following completion of each scheduled post-dose ECG at Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=48 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
T1/2 for serum deferiprone
|
1.8 hour
Standard Deviation 0.3
|
1.8 hour
Standard Deviation 0.3
|
—
|
—
|
|
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
T1/2 for serum deferiprone 3-O-glucuronide
|
2.5 hour
Standard Deviation 0.5
|
2.6 hour
Standard Deviation 0.2
|
—
|
—
|
SECONDARY outcome
Timeframe: 24-hour intervalPopulation: Cardiodynamic Analysis Set : all randomized subjects who received at least 1 dose of study medication and who had valid Day 1 QT/QTc interval measurements (predose and at least one postdose measurement).
Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.
Outcome measures
| Measure |
33 mg/kg Deferiprone
n=46 Participants
A single dose of deferiprone 500 mg tablets at a dosage of 33 mg/kg (the maximum therapeutic level), rounded to the nearest 250 mg. Subjects additionally received deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose, plus 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Placebo Control
n=45 Participants
A single dose of deferiprone -matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm C - Placebo Control
A single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Subjects additionally received 1 moxifloxacin-matching placebo tablet. Tablets were administered orally with approximately 240 mL of water.
|
Arm D - Positive Control
One 400 mg moxifloxacin tablet. Subjects additionally received a single dose of deferiprone-matching placebo tablets to provide the same total number of tablets as for a 50 mg/kg dose. Tablets were administered orally with approximately 240 mL of water.
|
|---|---|---|---|---|
|
Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of Moxifloxacin
|
14.7 milliseconds
Standard Deviation 6.38
|
1.2 milliseconds
Standard Deviation 6.46
|
—
|
—
|
Adverse Events
Treatment Arm A - Maximum Therapeutic Dose
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Treatment Arm B - Supratherapeutic Dose
Serious events: 0 serious events
Other events: 35 other events
Deaths: 0 deaths
Treatment Arm C - Placebo Control
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Treatment Arm D - Positive Control
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment Arm A - Maximum Therapeutic Dose
n=46 participants at risk
Single dose of 33 mg/kg rounded to the nearest 250 mg of deferiprone tablets, deferiprone matching placebo tablets and one moxifloxacin matching placebo tablet.
Deferiprone
deferiprone matching placebo tablets
moxifloxacin matching placebo tablet
|
Treatment Arm B - Supratherapeutic Dose
n=48 participants at risk
Single dose of 50 mg/kg rounded to the nearest 250 mg of deferiprone tablets, and one moxifloxacin matching placebo tablet.
Deferiprone
moxifloxacin matching placebo tablet
|
Treatment Arm C - Placebo Control
n=45 participants at risk
Single dose of deferiprone matching placebo tablets and one moxifloxacin matching placebo tablet.
deferiprone matching placebo tablets
moxifloxacin matching placebo tablet
|
Treatment Arm D - Positive Control
n=46 participants at risk
Single dose of deferiprone matching placebo tablets and one 400 mg moxifloxacin tablet.
Deferiprone
moxifloxacin
|
|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/45 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Dizziness
|
6.5%
3/46 • Number of events 3 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
12.5%
6/48 • Number of events 6 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/45 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Dizziness postural
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Formication
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Headache
|
17.4%
8/46 • Number of events 10 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
66.7%
32/48 • Number of events 34 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
15.6%
7/45 • Number of events 7 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
6.5%
3/46 • Number of events 3 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Cardiac disorders
Palpitations
|
2.2%
1/46 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
4.2%
2/48 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
4.4%
2/45 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Cardiac disorders
Sinus arrest
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Gastrointestinal disorders
Nausea
|
15.2%
7/46 • Number of events 8 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
39.6%
19/48 • Number of events 20 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
4.4%
2/45 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
2/46 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
29.2%
14/48 • Number of events 15 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
General disorders
Asthenia
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
General disorders
Chest discomfort
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/45 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
General disorders
Chills
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
4.2%
2/48 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
General disorders
Fatigue
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
General disorders
Feeling hot
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
8.3%
4/48 • Number of events 4 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
General disorders
Irritability
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
General disorders
Sensation of foreign body
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/45 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Injury, poisoning and procedural complications
Procedural dizziness
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Investigations
Electrocardiogram QRS complex prolonged
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/45 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Investigations
Electrocardiogram QT prolonged
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Investigations
Red blood cells urine positive
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Presyncope
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Somnolence
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Nervous system disorders
Syncope
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Psychiatric disorders
Abnormal dreams
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Psychiatric disorders
Anxiety
|
4.3%
2/46 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Renal and urinary disorders
Chromaturia
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
4.2%
2/48 • Number of events 2 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/45 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Reproductive system and breast disorders
Vaginal discharge
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal ulcer
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
2.2%
1/46 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/48 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
|
Vascular disorders
Pallor
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
2.1%
1/48 • Number of events 1 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/45 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
0.00%
0/46 • Adverse events were collected from the time of the first dose until 7 days (± 1 day) following the last study event of Period 4 or following early withdrawal.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee All unpublished information given to the CRO by ApoPharma shall not be published or disclosed to a third party without the prior written consent of ApoPharma. The data generated by this study are considered confidential information and the property of ApoPharma. This confidential information may be published only in collaboration with participating personnel from ApoPharma or upon ApoPharma written consent to publish the article.
- Publication restrictions are in place
Restriction type: OTHER