Trial Outcomes & Findings for Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload (NCT NCT01186419)
NCT ID: NCT01186419
Last Updated: 2021-06-10
Results Overview
LIC was determined by R2 Magnetic Resonance Imaging (MRI).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
51 participants
Primary outcome timeframe
Baseline and 96 weeks
Results posted on
2021-06-10
Participant Flow
Participant milestones
| Measure |
SPD602 16 mg/kg/Day
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
SPD602 32 mg/kg/Day
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
27
|
|
Overall Study
COMPLETED
|
17
|
18
|
|
Overall Study
NOT COMPLETED
|
7
|
9
|
Reasons for withdrawal
| Measure |
SPD602 16 mg/kg/Day
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
SPD602 32 mg/kg/Day
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
5
|
3
|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Physician Decision
|
0
|
3
|
|
Overall Study
Other
|
1
|
1
|
Baseline Characteristics
Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload
Baseline characteristics by cohort
| Measure |
SPD602 16 mg/kg/Day
n=24 Participants
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
SPD602 32 mg/kg/Day
n=27 Participants
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
50 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
28.7 years
STANDARD_DEVIATION 8.60 • n=99 Participants
|
28.4 years
STANDARD_DEVIATION 7.11 • n=107 Participants
|
28.5 years
STANDARD_DEVIATION 7.77 • n=206 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and 96 weeksPopulation: Full Analysis Set, defined as all subjects in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all subjects who received any amount of investigational product.
LIC was determined by R2 Magnetic Resonance Imaging (MRI).
Outcome measures
| Measure |
SPD602
n=26 Participants
Participants received SPD602 orally once daily for up to 96 weeks.
|
|---|---|
|
Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks
|
-1.75 mg/g
Standard Deviation 4.839
|
SECONDARY outcome
Timeframe: 92 weeksPopulation: Pharmacokinetic (PK) Analysis Set, defined as all subjects in the Safety Set for whom the primary PK data were considered sufficient and interpretable. The Safety Set was defined as all subjects who received any amount of investigational product.
Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administered.
Outcome measures
| Measure |
SPD602
n=5 Participants
Participants received SPD602 orally once daily for up to 96 weeks.
|
|---|---|
|
Maximum Plasma Concentration (Cmax) of SPD602
|
25702.7 ng/ml
Standard Deviation 4448.06
|
SECONDARY outcome
Timeframe: 92 weeksPopulation: PK Analysis Set, defined as all subjects in the Safety Set for whom the primary PK data were considered sufficient and interpretable. The Safety Set was defined as all subjects who received any amount of investigational product.
AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure of how much and how long a drug stays in a body.
Outcome measures
| Measure |
SPD602
n=5 Participants
Participants received SPD602 orally once daily for up to 96 weeks.
|
|---|---|
|
Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602
|
62998.6 ng*hr/ml
Standard Deviation 23094.72
|
Adverse Events
SPD602 16 mg/kg/d
Serious events: 3 serious events
Other events: 24 other events
Deaths: 0 deaths
SPD602 32 mg/kg/d
Serious events: 2 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SPD602 16 mg/kg/d
n=24 participants at risk
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
SPD602 32 mg/kg/d
n=27 participants at risk
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
|---|---|---|
|
Congenital, familial and genetic disorders
Sickle cell anemia with crisis
|
4.2%
1/24 • Number of events 4
|
0.00%
0/27
|
|
Gastrointestinal disorders
Vomiting
|
4.2%
1/24 • Number of events 1
|
0.00%
0/27
|
|
General disorders
Chest discomfort
|
0.00%
0/24
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/24
|
3.7%
1/27 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/24
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Hypoaesthesia
|
4.2%
1/24 • Number of events 1
|
0.00%
0/27
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/24
|
3.7%
1/27 • Number of events 1
|
Other adverse events
| Measure |
SPD602 16 mg/kg/d
n=24 participants at risk
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
SPD602 32 mg/kg/d
n=27 participants at risk
Participants received SPD602 orally once daily for up to 96 weeks. At Week 24, the iron clearing activity of SPD602 was assessed for each participant and the dose may have been adjusted to a higher or lower dose if the clinical response was deemed insufficient or too robust, respectively (maximum dose=60mg/kg/day; minimum dose=8mg/kg/day). Participants not dose adjusted at Week 24 may also have had later dose adjustments to a higher or lower dose.
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
8.3%
2/24 • Number of events 2
|
11.1%
3/27 • Number of events 4
|
|
Eye disorders
Conjunctivitis
|
8.3%
2/24 • Number of events 2
|
7.4%
2/27 • Number of events 2
|
|
Eye disorders
Ocular icterus
|
0.00%
0/24
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/24
|
18.5%
5/27 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
4/24 • Number of events 4
|
18.5%
5/27 • Number of events 7
|
|
Gastrointestinal disorders
Colitis
|
4.2%
1/24 • Number of events 1
|
7.4%
2/27 • Number of events 3
|
|
Gastrointestinal disorders
Constipation
|
4.2%
1/24 • Number of events 2
|
14.8%
4/27 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhea
|
4.2%
1/24 • Number of events 2
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
Dyspepsia
|
12.5%
3/24 • Number of events 3
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/24
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
Flatulence
|
20.8%
5/24 • Number of events 7
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
12.5%
3/24 • Number of events 3
|
11.1%
3/27 • Number of events 3
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/24
|
11.1%
3/27 • Number of events 4
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
2/24 • Number of events 3
|
7.4%
2/27 • Number of events 2
|
|
General disorders
Asthenia
|
12.5%
3/24 • Number of events 4
|
3.7%
1/27 • Number of events 4
|
|
General disorders
Fatigue
|
8.3%
2/24 • Number of events 2
|
3.7%
1/27 • Number of events 2
|
|
General disorders
Influenza like illness
|
8.3%
2/24 • Number of events 3
|
14.8%
4/27 • Number of events 9
|
|
General disorders
Pyrexia
|
16.7%
4/24 • Number of events 7
|
11.1%
3/27 • Number of events 6
|
|
Infections and infestations
Bronchitis
|
8.3%
2/24 • Number of events 2
|
7.4%
2/27 • Number of events 2
|
|
Infections and infestations
Gastroenteritis
|
12.5%
3/24 • Number of events 3
|
11.1%
3/27 • Number of events 3
|
|
Infections and infestations
Influenza
|
8.3%
2/24 • Number of events 5
|
22.2%
6/27 • Number of events 7
|
|
Infections and infestations
Nasopharyngitis
|
20.8%
5/24 • Number of events 5
|
14.8%
4/27 • Number of events 4
|
|
Infections and infestations
Pharyngitis
|
20.8%
5/24 • Number of events 5
|
18.5%
5/27 • Number of events 6
|
|
Infections and infestations
Pharyngotonsillitis
|
4.2%
1/24 • Number of events 1
|
7.4%
2/27 • Number of events 3
|
|
Infections and infestations
Respiratory tract infection viral
|
8.3%
2/24 • Number of events 2
|
7.4%
2/27 • Number of events 2
|
|
Infections and infestations
Sinusitis
|
12.5%
3/24 • Number of events 3
|
3.7%
1/27 • Number of events 2
|
|
Infections and infestations
Upper respiratory tract infection
|
20.8%
5/24 • Number of events 7
|
25.9%
7/27 • Number of events 13
|
|
Infections and infestations
Viral infection
|
4.2%
1/24 • Number of events 1
|
7.4%
2/27 • Number of events 2
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
4.2%
1/24 • Number of events 1
|
7.4%
2/27 • Number of events 2
|
|
Investigations
Blood creatinine increased
|
0.00%
0/24
|
11.1%
3/27 • Number of events 3
|
|
Investigations
Cardiac murmur
|
0.00%
0/24
|
14.8%
4/27 • Number of events 8
|
|
Investigations
Gamma-glutamyltransferase increased
|
4.2%
1/24 • Number of events 4
|
11.1%
3/27 • Number of events 3
|
|
Investigations
Transaminases increased
|
8.3%
2/24 • Number of events 2
|
18.5%
5/27 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.5%
3/24 • Number of events 5
|
7.4%
2/27 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
29.2%
7/24 • Number of events 10
|
14.8%
4/27 • Number of events 11
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.5%
3/24 • Number of events 3
|
0.00%
0/27
|
|
Nervous system disorders
Headache
|
33.3%
8/24 • Number of events 24
|
33.3%
9/27 • Number of events 15
|
|
Nervous system disorders
Paraesthesia
|
8.3%
2/24 • Number of events 5
|
14.8%
4/27 • Number of events 5
|
|
Renal and urinary disorders
Chromaturia
|
4.2%
1/24 • Number of events 1
|
7.4%
2/27 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
3/24 • Number of events 4
|
3.7%
1/27 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
16.7%
4/24 • Number of events 10
|
14.8%
4/27 • Number of events 7
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.3%
2/24 • Number of events 3
|
0.00%
0/27
|
|
Injury, poisoning and procedural complications
Joint injury
|
0.00%
0/24
|
7.4%
2/27 • Number of events 3
|
|
Injury, poisoning and procedural complications
Joint sprain
|
8.3%
2/24 • Number of events 2
|
0.00%
0/27
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Injury, poisoning and procedural complications
Contusion
|
8.3%
2/24 • Number of events 2
|
0.00%
0/27
|
|
General disorders
Oedema peripheral
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
8.3%
2/24 • Number of events 2
|
0.00%
0/27
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/24
|
7.4%
2/27 • Number of events 2
|
|
Infections and infestations
Cystitis
|
8.3%
2/24 • Number of events 2
|
0.00%
0/27
|
|
Infections and infestations
Oral herpes
|
8.3%
2/24 • Number of events 2
|
0.00%
0/27
|
|
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis
|
8.3%
2/24 • Number of events 7
|
0.00%
0/27
|
|
Nervous system disorders
Hypoaesthesia
|
8.3%
2/24 • Number of events 9
|
0.00%
0/27
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER