Trial Outcomes & Findings for Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera (NCT NCT00928707)
NCT ID: NCT00928707
Last Updated: 2019-10-31
Results Overview
The percentage of patients with overall (complete or partial) response at week 12 were assessed. · Complete response: 1. HCT (Hematocrit) \< 45% without phlebotomy, and 2. platelets ≤ 400 x109/L, and 3. WBC (white blood cell) ≤ 10 x 109/L, and 4. no splenomegaly, and 5. no disease related systemic symptoms (microvascular disturbances, pruritus, headache); · Partial response: 1. HCT \< 45% without phlebotomy, or 2. fulfilment of at least 3 of the other above mentioned criteria; · No response: any response that did not satisfy the criteria set for partial response.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
45 participants
Primary outcome timeframe
At week 12 of treatment
Results posted on
2019-10-31
Participant Flow
Participant milestones
| Measure |
GIVINOSTAT +Maximum Tolerated Dose (MTD) of Hydroxyurea (HU)_1
50 mg o.d. of GIVINOSTAT + maximum tolerated dose (MTD) of hydroxyurea (HU) monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + maximum tolerated dose (MTD) of Hydroxyurea (HU): 50 mg o.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy
|
GIVINOSTAT +Maximum Tolerated Dose (MTD) of Hydroxyurea (HU)_2
50 mg b.i.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + maximum tolerated dose (MTD) of Hydroxyurea (HU): 50 mg b.i.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy
|
|---|---|---|
|
Overall Study
STARTED
|
23
|
22
|
|
Overall Study
COMPLETED
|
22
|
22
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
GIVINOSTAT +Maximum Tolerated Dose (MTD) of Hydroxyurea (HU)_1
50 mg o.d. of GIVINOSTAT + maximum tolerated dose (MTD) of hydroxyurea (HU) monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + maximum tolerated dose (MTD) of Hydroxyurea (HU): 50 mg o.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy
|
GIVINOSTAT +Maximum Tolerated Dose (MTD) of Hydroxyurea (HU)_2
50 mg b.i.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + maximum tolerated dose (MTD) of Hydroxyurea (HU): 50 mg b.i.d. of GIVINOSTAT + maximum tolerated dose (MTD) of Hydroxyurea (HU) monotherapy
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera
Baseline characteristics by cohort
| Measure |
GIVINOSTAT + MTD Hydroxyurea_1
n=23 Participants
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
GIVINOSTAT + MTD Hydroxyurea_2
n=22 Participants
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
23 participants
n=5 Participants
|
22 participants
n=7 Participants
|
45 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At week 12 of treatmentPopulation: Safety/ITT population: included all randomized subjects who received at least one dose of study medication.
The percentage of patients with overall (complete or partial) response at week 12 were assessed. · Complete response: 1. HCT (Hematocrit) \< 45% without phlebotomy, and 2. platelets ≤ 400 x109/L, and 3. WBC (white blood cell) ≤ 10 x 109/L, and 4. no splenomegaly, and 5. no disease related systemic symptoms (microvascular disturbances, pruritus, headache); · Partial response: 1. HCT \< 45% without phlebotomy, or 2. fulfilment of at least 3 of the other above mentioned criteria; · No response: any response that did not satisfy the criteria set for partial response.
Outcome measures
| Measure |
GIVINOSTAT + MTD Hydroxyurea_1
n=22 Participants
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
GIVINOSTAT + MTD Hydroxyurea_2
n=22 Participants
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
|
|---|---|---|
|
Percentage of Patients With Overall Haematological Response at Week 12.
Responder
|
54.5 percentage of particpants
Interval 33.7 to 75.4
|
50.0 percentage of particpants
Interval 29.1 to 70.9
|
|
Percentage of Patients With Overall Haematological Response at Week 12.
Non responder
|
45.5 percentage of particpants
Interval 24.6 to 66.3
|
50.0 percentage of particpants
Interval 29.1 to 70.9
|
SECONDARY outcome
Timeframe: At week 24 of treatmentPopulation: Safety/Intention to treat (ITT) population included all randomized subjects who received at least one dose of study medication.
Haematological response after a 50 mg increase of the initial Givinostat dose in non-responder patients at the time when the primary endpoint was assessed (week 12). * Complete response: 1. HCT\< 45% without phlebotomy, and 2. platelets ≤ 400 x109/L, and 3. WBC ≤ 10 x 109/L, and 4. no splenomegaly, and 5. no disease related systemic symptoms (microvascular disturbances, pruritus, headache); * Partial response: 1. HCT \< 45% without phlebotomy, or 2. fulfilment of at least 3 of the other above mentioned criteria; * No response: any response that did not satisfy the criteria set for partial response.
Outcome measures
| Measure |
GIVINOSTAT + MTD Hydroxyurea_1
n=22 Participants
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
GIVINOSTAT + MTD Hydroxyurea_2
n=22 Participants
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
|
|---|---|---|
|
Percentage of Patients With Overall Haematological Response at Week 24 by Dose Escalation After Week 12.
Responder
|
63.6 percentage of participants
Interval 43.5 to 83.7
|
40.9 percentage of participants
Interval 20.4 to 61.5
|
|
Percentage of Patients With Overall Haematological Response at Week 24 by Dose Escalation After Week 12.
Non responder
|
36.4 percentage of participants
Interval 16.3 to 56.5
|
59.1 percentage of participants
Interval 38.5 to 79.6
|
SECONDARY outcome
Timeframe: At weeks 12, 24, at "drop out visit" and at "End of Study" (EOS). EOS stays for 7 days after last drug intake if patient is withdrawn from the study before week 24.Population: Safety/Intention-to-treat (ITT) population, which included all randomized subjects who received at least one dose of study medication.
To determine JAK2V617F mutational status, a quantitative RT-PCR (Real Time-Polymerase Chain Reaction) is executed on peripheral blood granulocyte and haematopoietic colonies (with and without hepatocyte growth factors - HGFs).
Outcome measures
| Measure |
GIVINOSTAT + MTD Hydroxyurea_1
n=22 Participants
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
GIVINOSTAT + MTD Hydroxyurea_2
n=21 Participants
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
|
|---|---|---|
|
Change From Baseline of the JAK2V617F Allele Burden by Quantitative RT-PCR
Week 12
|
-2.6 percent change
Standard Deviation 8.2
|
0.00 percent change
Standard Deviation 6.0
|
|
Change From Baseline of the JAK2V617F Allele Burden by Quantitative RT-PCR
Week 24
|
-3.8 percent change
Standard Deviation 11.5
|
4.6 percent change
Standard Deviation 5.7
|
|
Change From Baseline of the JAK2V617F Allele Burden by Quantitative RT-PCR
Drop-out
|
-4.0 percent change
Standard Deviation 0.00
|
-9.5 percent change
Standard Deviation 20.5
|
|
Change From Baseline of the JAK2V617F Allele Burden by Quantitative RT-PCR
EOS
|
-3.8 percent change
Standard Deviation 11.1
|
3.0 percent change
Standard Deviation 8.6
|
SECONDARY outcome
Timeframe: Baseline, at weeks 12 and 24Population: Safety/Intention-to-treat (ITT) population, which included all randomized subjects who received at least one dose of study medication.
JAK2V617F genotyping and quantification were performed on gradient-separated mononuclear cells during the pre-treatment evaluations (baseline), halfway through the study (12th weeks) and at the end of the study period (24th weeks). Baseline: n=22 (50 mg od); 22 (50 mg bid) Week 12: n=20 (50 mg od); 19 (50 mg bid) Week 24: n=18 (50 mg od); 18 (50 mg bid)
Outcome measures
| Measure |
GIVINOSTAT + MTD Hydroxyurea_1
n=22 Participants
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
GIVINOSTAT + MTD Hydroxyurea_2
n=22 Participants
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
|
|---|---|---|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
week 12 - heterozygous
|
25.0 percentage of participants
|
31.6 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
week 12 - homozygous
|
70.0 percentage of participants
|
63.2 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
week 12 - not done
|
5.0 percentage of participants
|
5.3 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
week 24 - heterozygous
|
22.2 percentage of participants
|
11.1 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
week 24 - homozygous
|
72.2 percentage of participants
|
77.8 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
week 24 - not done
|
5.6 percentage of participants
|
11.1 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
Baseline - heterozygous
|
27.3 percentage of participants
|
22.7 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
Baseline - homozygous
|
72.7 percentage of participants
|
72.7 percentage of participants
|
|
Percentage of Patients With a Reduction of the Fraction of JAK2V617F Positive Clonogenic Progenitor by Timepoints
Baseline - not done
|
0 percentage of participants
|
4.5 percentage of participants
|
Adverse Events
GIVINOSTAT + MTD Hydroxyurea_1
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
GIVINOSTAT + MTD Hydroxyurea_2
Serious events: 1 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
GIVINOSTAT + MTD Hydroxyurea_1
n=22 participants at risk
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
GIVINOSTAT + MTD Hydroxyurea_2
n=22 participants at risk
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
|
|---|---|---|
|
Surgical and medical procedures
Appendicectomy
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Respiratory, thoracic and mediastinal disorders
Embolism
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Social circumstances
Pregnancy of partner
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
Other adverse events
| Measure |
GIVINOSTAT + MTD Hydroxyurea_1
n=22 participants at risk
50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg o.d. + MTD Hydroxyurea: 50 mg o.d. of GIVINOSTAT + MTD of HU monotherapy
|
GIVINOSTAT + MTD Hydroxyurea_2
n=22 participants at risk
50 mg b.i.d. of GIVINOSTAT + MTD of HU monotherapy
GIVINOSTAT (ITF2357) 50 mg b.i.d. + MTD Hydroxyurea: 50 mg b.i.d. of GIVINOSTAT + MTD HU monotherapy
|
|---|---|---|
|
Vascular disorders
Haematoma
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Vascular disorders
Hypertension
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Vascular disorders
Phlebitis
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Vascular disorders
Thrombophlebitis superficial
|
4.5%
1/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Surgical and medical procedures
Curetting of chalazion
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
General disorders
Asthenia
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
General disorders
Fatigue
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
General disorders
Oedema
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
General disorders
Pyrexia
|
9.1%
2/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Psychiatric disorders
Panic attack
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Injury, poisoning and procedural complications
Injury
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Aspartate aminotransferase increased
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Blood alkaline phosphatase increased
|
4.5%
1/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Blood creatine phosphokinase increased
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Blood creatinine increased
|
13.6%
3/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 6 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Blood magnesium increased
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Blood tryglicerides increased
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 4 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Blood urea increased
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
Platelet count increased
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Investigations
White blood cell count increased
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Cardiac disorders
Arrhythmia
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Cardiac disorders
Tachycardia
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Blood and lymphatic system disorders
Anaemia
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
22.7%
5/22 • Number of events 5 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
31.8%
7/22 • Number of events 8 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Nervous system disorders
Dizziness
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Nervous system disorders
Headache
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Nervous system disorders
Paraesthesia
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Abdominal pain
|
13.6%
3/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
13.6%
3/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Constipation
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Diarrhoea
|
45.5%
10/22 • Number of events 12 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
31.8%
7/22 • Number of events 10 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Gastritis
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Haematochezia
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Nausea
|
13.6%
3/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Stomatitis
|
9.1%
2/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Tongue haemorrhage
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Renal and urinary disorders
Dysuria
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Skin and subcutaneous tissue disorders
Actinic keratosis
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
9.1%
2/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Endocrine disorders
Goitre
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
9.1%
2/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
9.1%
2/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Infections and infestations
Genitourinary tract infection
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 2 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Infections and infestations
Influenza
|
13.6%
3/22 • Number of events 3 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Infections and infestations
Pharyngitis
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Infections and infestations
Rhinitis
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
|
Infections and infestations
Urogenital infection fungal
|
0.00%
0/22 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
4.5%
1/22 • Number of events 1 • Adverse events (AEs) were recorded at weeks 1 ,3, 6, 9, 12, 16, 20 or end of treatment visit (week 24 or 7 days after last drug intake)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place