Trial Outcomes & Findings for Long-term, Safety, Tolerability and Efficacy Study of AFQ056 in Adult Patients With Fragile X Syndrome (NCT NCT01348087)

NCT ID: NCT01348087

Last Updated: 2016-05-25

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 patients 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 patients 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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

148 participants

Primary outcome timeframe

Prior to first dose in extension study, Baseline (start of study treatment in extension study) to End of trial

Results posted on

2016-05-25

Participant Flow

The study was conducted at 28 centers in 10 countries

A total of 148 patients were enrolled and treated, including 1 patient who discontinued and was later re-enrolled under a new patient number. Category 1 patients received AFQ056 in the core study and enrolled in the extension within 7 days of completing the core study; Category 2 included all other patients enrolled into the extension study

Participant milestones

Participant milestones
Measure
AFQ056 Total
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
148
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
148

Reasons for withdrawal

Reasons for withdrawal
Measure
AFQ056 Total
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
Unsatisfactory therapeutic effect
35
Overall Study
Administrative problems
79
Overall Study
protocol deviation
1
Overall Study
Lost to Follow-up
1
Overall Study
Subject withdrew consent
7
Overall Study
Adverse Event
25

Baseline Characteristics

Long-term, Safety, Tolerability and Efficacy Study of AFQ056 in Adult Patients With Fragile X Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
AFQ056
n=148 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
26.6 Years
STANDARD_DEVIATION 6.85 • n=99 Participants
Sex: Female, Male
Female
10 Participants
n=99 Participants
Sex: Female, Male
Male
138 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 trial

Population: 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 patients 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 patients 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

Outcome measures
Measure
Prior to Ext First Dose
n=40 Participants
AFQ056 25mg Bid
n=147 Participants
AFQ056 50mg Bid
n=148 Participants
AFQ056 75mg Bid
n=141 Participants
AFQ056 100mg Bid
n=135 Participants
AFQ056 Total
n=148 Participants
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
At least one AE
9 Participants
49 Participants
47 Participants
50 Participants
112 Participants
138 Participants
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
At least one severe AE
1 Participants
1 Participants
2 Participants
5 Participants
18 Participants
24 Participants
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
Any serious or significant AE
0 Participants
1 Participants
0 Participants
1 Participants
6 Participants
7 Participants
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
SAE
0 Participants
1 Participants
0 Participants
1 Participants
6 Participants
7 Participants
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
Discontinued due to SAE
0 Participants
1 Participants
0 Participants
1 Participants
1 Participants
3 Participants
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs).
Discontinued due to non serious AE
0 Participants
4 Participants
5 Participants
4 Participants
11 Participants
22 Participants

Adverse Events

Prior to Ext.First Dose

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

AFQ056 25 mg Bid

Serious events: 1 serious events
Other events: 26 other events
Deaths: 0 deaths

AFQ056 50 mg Bid

Serious events: 0 serious events
Other events: 28 other events
Deaths: 0 deaths

AFQ056 75 mg Bid

Serious events: 1 serious events
Other events: 36 other events
Deaths: 0 deaths

AFQ056 100 mg Bid

Serious events: 6 serious events
Other events: 88 other events
Deaths: 0 deaths

AFQ056 Total

Serious events: 7 serious events
Other events: 117 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Prior to Ext.First Dose
n=40 participants at risk
Prior to Ext.first dose
AFQ056 25 mg Bid
n=147 participants at risk
AFQ056 25 mg bid
AFQ056 50 mg Bid
n=148 participants at risk
AFQ056 50 mg bid
AFQ056 75 mg Bid
n=141 participants at risk
AFQ056 75 mg bid
AFQ056 100 mg Bid
n=135 participants at risk
AFQ056 100 mg bid
AFQ056 Total
n=148 participants at risk
Investigations
Hepatic enzyme increased
0.00%
0/40
0.00%
0/147
0.00%
0/148
0.00%
0/141
0.74%
1/135
0.68%
1/148
Nervous system disorders
Epilepsy
0.00%
0/40
0.00%
0/147
0.00%
0/148
0.00%
0/141
0.74%
1/135
0.68%
1/148
Psychiatric disorders
Aggression
0.00%
0/40
0.00%
0/147
0.00%
0/148
0.71%
1/141
1.5%
2/135
2.0%
3/148
Psychiatric disorders
Agitation
0.00%
0/40
0.00%
0/147
0.00%
0/148
0.00%
0/141
1.5%
2/135
1.4%
2/148
Psychiatric disorders
Hallucination, auditory
0.00%
0/40
0.00%
0/147
0.00%
0/148
0.00%
0/141
0.74%
1/135
0.68%
1/148
Psychiatric disorders
Hallucination, visual
0.00%
0/40
0.68%
1/147
0.00%
0/148
0.00%
0/141
0.74%
1/135
0.68%
1/148
Psychiatric disorders
Panic attack
0.00%
0/40
0.00%
0/147
0.00%
0/148
0.00%
0/141
0.74%
1/135
0.68%
1/148

Other adverse events

Other adverse events
Measure
Prior to Ext.First Dose
n=40 participants at risk
Prior to Ext.first dose
AFQ056 25 mg Bid
n=147 participants at risk
AFQ056 25 mg bid
AFQ056 50 mg Bid
n=148 participants at risk
AFQ056 50 mg bid
AFQ056 75 mg Bid
n=141 participants at risk
AFQ056 75 mg bid
AFQ056 100 mg Bid
n=135 participants at risk
AFQ056 100 mg bid
AFQ056 Total
n=148 participants at risk
Gastrointestinal disorders
Diarrhoea
0.00%
0/40
0.68%
1/147
0.68%
1/148
0.71%
1/141
5.2%
7/135
6.8%
10/148
Gastrointestinal disorders
Vomiting
0.00%
0/40
0.68%
1/147
1.4%
2/148
1.4%
2/141
10.4%
14/135
12.2%
18/148
General disorders
Asthenia
0.00%
0/40
0.68%
1/147
0.00%
0/148
3.5%
5/141
5.9%
8/135
6.1%
9/148
General disorders
Fatigue
0.00%
0/40
0.68%
1/147
1.4%
2/148
2.1%
3/141
2.2%
3/135
6.1%
9/148
Infections and infestations
Nasopharyngitis
7.5%
3/40
1.4%
2/147
2.7%
4/148
2.1%
3/141
15.6%
21/135
18.2%
27/148
Infections and infestations
Upper respiratory tract infection
0.00%
0/40
2.7%
4/147
0.68%
1/148
2.1%
3/141
11.9%
16/135
16.2%
24/148
Nervous system disorders
Dizziness
2.5%
1/40
3.4%
5/147
2.7%
4/148
0.71%
1/141
3.7%
5/135
8.8%
13/148
Nervous system disorders
Headache
0.00%
0/40
2.7%
4/147
2.0%
3/148
5.0%
7/141
10.4%
14/135
14.2%
21/148
Psychiatric disorders
Aggression
0.00%
0/40
4.1%
6/147
5.4%
8/148
3.5%
5/141
8.1%
11/135
14.9%
22/148
Psychiatric disorders
Agitation
0.00%
0/40
0.00%
0/147
0.68%
1/148
2.1%
3/141
7.4%
10/135
8.8%
13/148
Psychiatric disorders
Anxiety
0.00%
0/40
0.68%
1/147
2.0%
3/148
2.1%
3/141
7.4%
10/135
10.8%
16/148
Psychiatric disorders
Insomnia
2.5%
1/40
2.7%
4/147
2.0%
3/148
5.0%
7/141
8.9%
12/135
15.5%
23/148
Psychiatric disorders
Irritability
2.5%
1/40
0.00%
0/147
4.7%
7/148
2.8%
4/141
4.4%
6/135
10.1%
15/148
Respiratory, thoracic and mediastinal disorders
Cough
2.5%
1/40
2.7%
4/147
0.00%
0/148
1.4%
2/141
6.7%
9/135
10.8%
16/148

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

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 or disclosure of trial results in their entirety
  • Publication restrictions are in place

Restriction type: OTHER