Trial Outcomes & Findings for A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease (NCT NCT00446550)
NCT ID: NCT00446550
Last Updated: 2018-08-15
Results Overview
A TEAE was defined as any adverse event (AE) with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up (Day 183) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
Day 1 (after dosing) through Day 183
Results posted on
2018-08-15
Participant Flow
Confirmatory β-glucosidase (GBA) genotype testing was done at screening to confirm reported genotype (with the exception of participants enrolled in Israel).19 participants received at least 1 dose of study drug. All participants were eligible for inclusion in both the safety and the pharmacodynamics (PD) populations.
Participant milestones
| Measure |
Afegostat Tartrate Treatment Regimen 1
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
|
Afegostat Tartrate Treatment Regimen 2
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
8
|
|
Overall Study
Safety Population
|
11
|
8
|
|
Overall Study
PD Population
|
11
|
8
|
|
Overall Study
COMPLETED
|
10
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Afegostat Tartrate Treatment Regimen 1
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
|
Afegostat Tartrate Treatment Regimen 2
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease
Baseline characteristics by cohort
| Measure |
Afegostat Tartrate Treatment Regimen 1
n=11 Participants
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
|
Afegostat Tartrate Treatment Regimen 2
n=8 Participants
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43 years
STANDARD_DEVIATION 16.27 • n=99 Participants
|
39.1 years
STANDARD_DEVIATION 17.62 • n=107 Participants
|
41.4 years
STANDARD_DEVIATION 16.48 • n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 1 (after dosing) through Day 183Population: Safety Population: all participants who received at least 1 dose of study drug.
A TEAE was defined as any adverse event (AE) with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up (Day 183) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Afegostat Tartrate Treatment Regimen 1
n=11 Participants
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
|
Afegostat Tartrate Treatment Regimen 2
n=8 Participants
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
|
|---|---|---|
|
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 169Population: PD Population: all participants who were included in the Safety Population and had a baseline and at least 1 post-baseline PD measurement.
GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug.
Outcome measures
| Measure |
Afegostat Tartrate Treatment Regimen 1
n=11 Participants
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
|
Afegostat Tartrate Treatment Regimen 2
n=7 Participants
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
|
|---|---|---|
|
Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
|
10.2 picomole/minute/mg
Standard Deviation 15.87
|
3.9 picomole/minute/mg
Standard Deviation 4.12
|
Adverse Events
Afegostat Tartrate Treatment Regimen 1
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Afegostat Tartrate Treatment Regimen 2
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Afegostat Tartrate Treatment Regimen 1
n=11 participants at risk
For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks.
|
Afegostat Tartrate Treatment Regimen 2
n=8 participants at risk
Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Abnormal sensation in eye
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Chalazion
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Conjunctival irritation
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Conjunctivitis
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Dry eye
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
25.0%
2/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Eye inflammation
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Eye irritation
|
18.2%
2/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Eye pruritus
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Lacrimation increased
|
27.3%
3/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Eye disorders
Vision blurred
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Abdominal pain
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Anal fissure
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Oral pain
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Tooth impacted
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Toothache
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
General disorders
Adverse drug reaction
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
General disorders
Fatigue
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Hepatobiliary disorders
Cholelithiasis
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Infections and infestations
Eyelid infection
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Infections and infestations
Fungal rash
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Infections and infestations
Gastroenteritis viral
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Infections and infestations
Influenza
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Infections and infestations
Upper respiratory tract infection
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Injury, poisoning and procedural complications
Contusion
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Investigations
Bacteria urine
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Investigations
Vitamin B12 decreased
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
18.2%
2/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Musculoskeletal and connective tissue disorders
Spinal disorder
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Nervous system disorders
Dizziness
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Nervous system disorders
Headache
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Nervous system disorders
Poor quality sleep
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Reproductive system and breast disorders
Menstrual disorder
|
25.0%
1/4 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract congestion
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Blister
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
|
Vascular disorders
Haematoma
|
0.00%
0/11 • Day 1 (after dosing) to Day 183
|
12.5%
1/8 • Day 1 (after dosing) to Day 183
|
|
Vascular disorders
Hypertension
|
9.1%
1/11 • Day 1 (after dosing) to Day 183
|
0.00%
0/8 • Day 1 (after dosing) to Day 183
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator can publish only the results from this trial, provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review prior to submission for publication. If requested and prior to publication, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER