Trial Outcomes & Findings for Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label) (NCT NCT01433354)
NCT ID: NCT01433354
Last Updated: 2016-03-24
Results Overview
Adverse events were summarized for the open-label treatment period, where the open-label treatment period is defined based on how AEs were collected and reported according to the manner in which participants entered the current study and which treatment (AFQ056 or placebo) they were receiving in the previous study. AEs which were continuing from the core study or that started after the end of core study but prior to first dose of open-label study medication in the extension study for Category 1 participants are shown under 'Prior to Ext. first dose'. AEs which started during the open-label treatment period are presented based on the last AFQ056 dose taken on or before the onset date of the AE (25 mg bid; 50 mg bid; 75 mg bid; or 100 mg bid). No efficacy data presented as study was terminated.
TERMINATED
PHASE2/PHASE3
119 participants
Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial
2016-03-24
Participant Flow
The study was conducted at 28 centres in 13 countries.
A total of 120 patients were enrolled, of which 119 received the study medication. Category 1 patients received AFQ056 in the core study and enrolled in the extension within 7 days of the core study; Category 2 included all other patients who were enrolled into the extension study
Participant milestones
| Measure |
AFQ056
Participants from a previous AFQ056 study who entered the open-label extension study were administered AFQ056 capsules at a starting dose of 25 milligram (mg) twice daily (bid) and then titrated to 50 mg bid, 75 mg bid and 100 mg bid at weekly intervals.
|
|---|---|
|
Overall Study
STARTED
|
119
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
119
|
Reasons for withdrawal
| Measure |
AFQ056
Participants from a previous AFQ056 study who entered the open-label extension study were administered AFQ056 capsules at a starting dose of 25 milligram (mg) twice daily (bid) and then titrated to 50 mg bid, 75 mg bid and 100 mg bid at weekly intervals.
|
|---|---|
|
Overall Study
Adverse Event
|
6
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Administrative problems
|
90
|
|
Overall Study
Protocol Violation
|
2
|
|
Overall Study
Lack of Efficacy
|
17
|
|
Overall Study
Subject Withdrew Consent
|
3
|
Baseline Characteristics
Long-term, Safety and Tolerability Study of AFQ056 in Adolescent Patients With Fragile X Syndrome (Open-label)
Baseline characteristics by cohort
| Measure |
AFQ056
n=119 Participants
Participants from a previous AFQ056 study who entered the open-label extension study were administered AFQ056 capsules at a starting dose of 25 milligram (mg) twice daily (bid) and then titrated to 50 mg bid, 75 mg bid and 100 mg bid at weekly intervals.
|
|---|---|
|
Age, Continuous
|
15.2 years
STANDARD_DEVIATION 1.75 • n=99 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
106 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trialPopulation: The analysis was performed in the safety set (SS) population, defined as participants who received at least one dose of study medication and had at least one safety assessment occurring after first dose of extension study medication. Here, 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.
Adverse events were summarized for the open-label treatment period, where the open-label treatment period is defined based on how AEs were collected and reported according to the manner in which participants entered the current study and which treatment (AFQ056 or placebo) they were receiving in the previous study. AEs which were continuing from the core study or that started after the end of core study but prior to first dose of open-label study medication in the extension study for Category 1 participants are shown under 'Prior to Ext. first dose'. AEs which started during the open-label treatment period are presented based on the last AFQ056 dose taken on or before the onset date of the AE (25 mg bid; 50 mg bid; 75 mg bid; or 100 mg bid). No efficacy data presented as study was terminated.
Outcome measures
| Measure |
AFQ056
n=119 Participants
Total
|
Prior to Ext. First Dose
n=31 Participants
|
AFQ056 25 mg Bid
n=119 Participants
|
AFQ056 50 mg Bid
n=118 Participants
|
AFQ056 75 mg Bid
n=116 Participants
|
AFQ056 100 mg Bid
n=108 Participants
|
|---|---|---|---|---|---|---|
|
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
At least one AE
|
110 participants
|
10 participants
|
36 participants
|
41 participants
|
44 participants
|
90 participants
|
|
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
4 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
3 participants
|
|
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Discontinued due to SAEs
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
At least one severe AE
|
8 participants
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
5 participants
|
|
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any serious or significant AE
|
4 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
3 participants
|
|
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Discontinued due to AEs
|
6 participants
|
1 participants
|
2 participants
|
2 participants
|
0 participants
|
3 participants
|
|
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Discontinued due to non serious AE
|
5 participants
|
1 participants
|
2 participants
|
2 participants
|
0 participants
|
2 participants
|
Adverse Events
Prior to Ext.First Dose
AFQ056 25 mg Bid
AFQ056 50 mg Bid
AFQ056 75 mg Bid
AFQ056 100 mg Bid
Total
Serious adverse events
| Measure |
Prior to Ext.First Dose
n=31 participants at risk
Prior to Ext.first dose
|
AFQ056 25 mg Bid
n=119 participants at risk
AFQ056 25 mg bid
|
AFQ056 50 mg Bid
n=118 participants at risk
AFQ056 50 mg bid
|
AFQ056 75 mg Bid
n=116 participants at risk
AFQ056 75 mg bid
|
AFQ056 100 mg Bid
n=108 participants at risk
AFQ056 100 mg bid
|
Total
n=119 participants at risk
Total
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Appendicitis
|
0.00%
0/31
|
0.00%
0/119
|
0.00%
0/118
|
0.00%
0/116
|
0.93%
1/108
|
0.84%
1/119
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/31
|
0.00%
0/119
|
0.00%
0/118
|
0.00%
0/116
|
0.93%
1/108
|
0.84%
1/119
|
|
Injury, poisoning and procedural complications
Foreign body
|
0.00%
0/31
|
0.00%
0/119
|
0.85%
1/118
|
0.00%
0/116
|
0.00%
0/108
|
0.84%
1/119
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/31
|
0.00%
0/119
|
0.00%
0/118
|
0.00%
0/116
|
0.93%
1/108
|
0.84%
1/119
|
|
Psychiatric disorders
Aggression
|
0.00%
0/31
|
0.00%
0/119
|
0.00%
0/118
|
0.00%
0/116
|
0.93%
1/108
|
0.84%
1/119
|
Other adverse events
| Measure |
Prior to Ext.First Dose
n=31 participants at risk
Prior to Ext.first dose
|
AFQ056 25 mg Bid
n=119 participants at risk
AFQ056 25 mg bid
|
AFQ056 50 mg Bid
n=118 participants at risk
AFQ056 50 mg bid
|
AFQ056 75 mg Bid
n=116 participants at risk
AFQ056 75 mg bid
|
AFQ056 100 mg Bid
n=108 participants at risk
AFQ056 100 mg bid
|
Total
n=119 participants at risk
Total
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
3.2%
1/31
|
1.7%
2/119
|
3.4%
4/118
|
0.00%
0/116
|
4.6%
5/108
|
10.1%
12/119
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
1/31
|
1.7%
2/119
|
4.2%
5/118
|
0.00%
0/116
|
7.4%
8/108
|
10.9%
13/119
|
|
General disorders
Fatigue
|
0.00%
0/31
|
1.7%
2/119
|
1.7%
2/118
|
2.6%
3/116
|
4.6%
5/108
|
9.2%
11/119
|
|
General disorders
Pyrexia
|
0.00%
0/31
|
0.00%
0/119
|
0.85%
1/118
|
1.7%
2/116
|
3.7%
4/108
|
5.9%
7/119
|
|
Infections and infestations
Ear infection
|
0.00%
0/31
|
1.7%
2/119
|
0.00%
0/118
|
0.86%
1/116
|
4.6%
5/108
|
6.7%
8/119
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/31
|
0.00%
0/119
|
1.7%
2/118
|
0.86%
1/116
|
4.6%
5/108
|
6.7%
8/119
|
|
Infections and infestations
Influenza
|
0.00%
0/31
|
0.84%
1/119
|
0.00%
0/118
|
1.7%
2/116
|
5.6%
6/108
|
6.7%
8/119
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/31
|
5.9%
7/119
|
2.5%
3/118
|
6.9%
8/116
|
23.1%
25/108
|
29.4%
35/119
|
|
Infections and infestations
Upper respiratory tract infection
|
3.2%
1/31
|
2.5%
3/119
|
4.2%
5/118
|
2.6%
3/116
|
8.3%
9/108
|
14.3%
17/119
|
|
Investigations
Weight increased
|
3.2%
1/31
|
0.84%
1/119
|
0.00%
0/118
|
0.00%
0/116
|
4.6%
5/108
|
5.9%
7/119
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.5%
2/31
|
0.00%
0/119
|
1.7%
2/118
|
0.86%
1/116
|
0.00%
0/108
|
4.2%
5/119
|
|
Nervous system disorders
Headache
|
0.00%
0/31
|
3.4%
4/119
|
0.85%
1/118
|
3.4%
4/116
|
7.4%
8/108
|
12.6%
15/119
|
|
Nervous system disorders
Psychomotor hyperactivity
|
0.00%
0/31
|
1.7%
2/119
|
2.5%
3/118
|
0.86%
1/116
|
2.8%
3/108
|
7.6%
9/119
|
|
Psychiatric disorders
Aggression
|
0.00%
0/31
|
2.5%
3/119
|
2.5%
3/118
|
3.4%
4/116
|
11.1%
12/108
|
16.0%
19/119
|
|
Psychiatric disorders
Agitation
|
0.00%
0/31
|
0.84%
1/119
|
0.85%
1/118
|
0.00%
0/116
|
3.7%
4/108
|
5.0%
6/119
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/31
|
2.5%
3/119
|
0.85%
1/118
|
0.00%
0/116
|
10.2%
11/108
|
12.6%
15/119
|
|
Psychiatric disorders
Initial insomnia
|
0.00%
0/31
|
2.5%
3/119
|
1.7%
2/118
|
3.4%
4/116
|
8.3%
9/108
|
15.1%
18/119
|
|
Psychiatric disorders
Insomnia
|
3.2%
1/31
|
3.4%
4/119
|
8.5%
10/118
|
4.3%
5/116
|
11.1%
12/108
|
21.0%
25/119
|
|
Psychiatric disorders
Irritability
|
0.00%
0/31
|
2.5%
3/119
|
0.85%
1/118
|
2.6%
3/116
|
8.3%
9/108
|
12.6%
15/119
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/31
|
0.84%
1/119
|
0.85%
1/118
|
3.4%
4/116
|
6.5%
7/108
|
10.1%
12/119
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/31
|
0.00%
0/119
|
1.7%
2/118
|
1.7%
2/116
|
2.8%
3/108
|
5.0%
6/119
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single- site are postponed until the publication of the pooled data (i.e, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER