Age-Related Memory Disorders
Conditions
Brief summary
The purpose of the study is to determine the safety, tolerability, and effectiveness of 2 dose levels of LX6171 given over 28 days in patients with Age Associated Memory Impairment (AAMI).
Interventions
DRUGLX6171 High Dose
A high dose of LX6171, using an oral suspension; daily oral intake for 28 days in the morning at approximately the same time.
DRUGLX6171 Low Dose
A low dose of LX6171, using an oral suspension; daily oral intake for 28 days in the morning at approximately the same time.
DRUGPlacebo
Matching placebo dosing with daily oral intake for 28 days in the morning at approximately the same time.
Sponsors
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Males and females aged 60-80 years old. * Complaints of memory loss in everyday life * Non-smokers or very light smokers (no more than 10 cigarettes/day) * Negative urine screen for drugs of abuse * Ability to provide written informed consent
Exclusion criteria
* History or evidence of any disease, disorder or injury that could cause cognitive deterioration. * Need for medications other than hormone replacement therapy, daily vitamins, or over-the-counter pain killers * Clinically significant abnormality on electrocardiogram * History of alcoholism or drug dependence * Use of dietary supplements containing Huperzine A, gingko biloba, phosphatidylserine, or Docosahexaenoic acid (DHA)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Exposed to LX6171 | ≥28 days | — |
| Number of Subjects Reporting at Least One Adverse Event (AE) | 28 days | An adverse event includes any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to study medication. |
| Number of Subjects Reporting Adverse Events Leading to Withdrawal | 28 days | — |
| Treatment Compliance | End of study | Subjects were considered compliant if they had taken \>70% of possible doses of the study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pittsburgh Sleep Quality Index at Day 28 | Day 28 | The Pittsburgh Sleep Quality Index is a self-rated questionnaire that assesses sleep quality and disturbances. Responses were scored on a scale of 0 to 3 where 3 is the negative extreme. Baseline (Day -1) scores were subtracted from Day 28 scores to obtain score change from baseline. |
| Plasma Concentration | Day 28 | — |
| Change From Baseline in Epworth Sleepiness Scale at Day 28 | Day 28 | The Epworth Sleepiness Scale is a self-administered questionnaire used to help quantify a subject's level of daytime sleepiness. Subjects recorded their chances of dozing on a scale of 0 to 3, with 0 being no chance and 3 being a high chance. Baseline (Day -1) scores were subtracted from Day 28 scores to obtain score change from baseline. |
| Change From Baseline (Day -1) in 15-Words Test: Acquisition Score at Day 28 | Day 28 | The 15-Words Test is used to measure verbal learning and memory. Subjects are scored on the number of recognized words on a scale of 0-15, with 0 being the worst and 15 being the best. The baseline (Day -1) score was subtracted from the Day 28 score to obtain the Score Change from Baseline. |
| Change From Baseline in 15-Word Test: Short-Term Delayed Recall Score at Day 28 | Day 28 | Subjects are asked to recall words from the preceding week's 15-Words Test. Baseline (Day -1) scores (scale 0-15, 0 being the worst) were subtracted from Day 28 scores to obtain the score change from baseline. |
| Change From Baseline in Memory Assessment Clinics Self-Rating Scale Total Score at Day 28 | Day 28 | The subjects were asked to describe their memory ability in a variety of situations of everyday life (a list of 25 questions) using a 5-point scale, with a lower score being a negative assessment. Baseline (Day -1) scores were subtracted from Day 28 scores to obtain score change from baseline. |
Countries
Netherlands
Participant flow
Recruitment details
The study was performed at 2 centers in the Netherlands, one in Utrecht and one in Zuidlaren. Recruitment began in October of 2007 and the last subject completed the study in October of 2008.
Participants by arm
| Arm | Count |
|---|---|
| High Dose 240 mg LX6171 oral suspension administered once per day | 35 |
| Low Dose 120 mg LX6171 oral suspension administered once per day | 36 |
| Placebo Placebo dosing volume-matched and administered once per day | 32 |
| Total | 103 |
Baseline characteristics
| Characteristic | High Dose | Low Dose | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 65.97 years STANDARD_DEVIATION 3.48 | 67.81 years STANDARD_DEVIATION 4.79 | 67.37 years STANDARD_DEVIATION 4.41 | 67.05 years STANDARD_DEVIATION 4.3 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 34 Participants | 36 Participants | 31 Participants | 101 Participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 12 Participants | 44 Participants |
| Sex: Female, Male Male | 19 Participants | 20 Participants | 20 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 25 / 35 | 22 / 36 | 26 / 32 |
| serious Total, serious adverse events | 0 / 35 | 0 / 36 | 0 / 32 |
Outcome results
Primary
Number of Participants Who Were Exposed to LX6171
Time frame: 14 to18 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | Number of Participants Who Were Exposed to LX6171 | 0 Participants |
| Low Dose | Number of Participants Who Were Exposed to LX6171 | 1 Participants |
| Placebo | Number of Participants Who Were Exposed to LX6171 | 0 Participants |
Primary
Number of Participants Who Were Exposed to LX6171
Time frame: ≥28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | Number of Participants Who Were Exposed to LX6171 | 35 Participants |
| Low Dose | Number of Participants Who Were Exposed to LX6171 | 33 Participants |
| Placebo | Number of Participants Who Were Exposed to LX6171 | 31 Participants |
Primary
Number of Participants Who Were Exposed to LX6171
Time frame: 25 to 27 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | Number of Participants Who Were Exposed to LX6171 | 0 Participants |
| Low Dose | Number of Participants Who Were Exposed to LX6171 | 2 Participants |
| Placebo | Number of Participants Who Were Exposed to LX6171 | 1 Participants |
Primary
Number of Subjects Reporting Adverse Events Leading to Withdrawal
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | Number of Subjects Reporting Adverse Events Leading to Withdrawal | 0 Participants |
| Low Dose | Number of Subjects Reporting Adverse Events Leading to Withdrawal | 1 Participants |
| Placebo | Number of Subjects Reporting Adverse Events Leading to Withdrawal | 0 Participants |
Primary
Number of Subjects Reporting at Least One Adverse Event (AE)
An adverse event includes any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not associated with the study medication and whether or not considered related to study medication.
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose | Number of Subjects Reporting at Least One Adverse Event (AE) | 25 Participants |
| Low Dose | Number of Subjects Reporting at Least One Adverse Event (AE) | 22 Participants |
| Placebo | Number of Subjects Reporting at Least One Adverse Event (AE) | 26 Participants |
Primary
Treatment Compliance
Subjects were considered compliant if they had taken \>70% of possible doses of the study drug.
Time frame: End of study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Treatment Compliance | 100.0 Percentage of Participants | Standard Deviation 0 |
| Low Dose | Treatment Compliance | 99.80 Percentage of Participants | Standard Deviation 0.84 |
| Placebo | Treatment Compliance | 99.89 Percentage of Participants | Standard Deviation 0.64 |
Secondary
Change From Baseline (Day -1) in 15-Words Test: Acquisition Score at Day 28
The 15-Words Test is used to measure verbal learning and memory. Subjects are scored on the number of recognized words on a scale of 0-15, with 0 being the worst and 15 being the best. The baseline (Day -1) score was subtracted from the Day 28 score to obtain the Score Change from Baseline.
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change From Baseline (Day -1) in 15-Words Test: Acquisition Score at Day 28 | -1.2 Number of words | Standard Deviation 7.6 |
| Low Dose | Change From Baseline (Day -1) in 15-Words Test: Acquisition Score at Day 28 | -1.9 Number of words | Standard Deviation 5.6 |
| Placebo | Change From Baseline (Day -1) in 15-Words Test: Acquisition Score at Day 28 | -1.1 Number of words | Standard Deviation 6.8 |
Secondary
Change From Baseline in 15-Word Test: Short-Term Delayed Recall Score at Day 28
Subjects are asked to recall words from the preceding week's 15-Words Test. Baseline (Day -1) scores (scale 0-15, 0 being the worst) were subtracted from Day 28 scores to obtain the score change from baseline.
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change From Baseline in 15-Word Test: Short-Term Delayed Recall Score at Day 28 | -1.5 Number of words | Standard Deviation 2.3 |
| Low Dose | Change From Baseline in 15-Word Test: Short-Term Delayed Recall Score at Day 28 | -1.7 Number of words | Standard Deviation 2.2 |
| Placebo | Change From Baseline in 15-Word Test: Short-Term Delayed Recall Score at Day 28 | -2.3 Number of words | Standard Deviation 2.6 |
Secondary
Change From Baseline in Epworth Sleepiness Scale at Day 28
The Epworth Sleepiness Scale is a self-administered questionnaire used to help quantify a subject's level of daytime sleepiness. Subjects recorded their chances of dozing on a scale of 0 to 3, with 0 being no chance and 3 being a high chance. Baseline (Day -1) scores were subtracted from Day 28 scores to obtain score change from baseline.
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change From Baseline in Epworth Sleepiness Scale at Day 28 | -0.9 Units on a scale | Standard Deviation 2 |
| Low Dose | Change From Baseline in Epworth Sleepiness Scale at Day 28 | 0 Units on a scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline in Epworth Sleepiness Scale at Day 28 | -0.6 Units on a scale | Standard Deviation 2.1 |
Secondary
Change From Baseline in Memory Assessment Clinics Self-Rating Scale Total Score at Day 28
The subjects were asked to describe their memory ability in a variety of situations of everyday life (a list of 25 questions) using a 5-point scale, with a lower score being a negative assessment. Baseline (Day -1) scores were subtracted from Day 28 scores to obtain score change from baseline.
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change From Baseline in Memory Assessment Clinics Self-Rating Scale Total Score at Day 28 | 0.9 Units on a scale | Standard Deviation 5.9 |
| Low Dose | Change From Baseline in Memory Assessment Clinics Self-Rating Scale Total Score at Day 28 | -2.4 Units on a scale | Standard Deviation 6 |
| Placebo | Change From Baseline in Memory Assessment Clinics Self-Rating Scale Total Score at Day 28 | 2.5 Units on a scale | Standard Deviation 6 |
Secondary
Change From Baseline in Pittsburgh Sleep Quality Index at Day 28
The Pittsburgh Sleep Quality Index is a self-rated questionnaire that assesses sleep quality and disturbances. Responses were scored on a scale of 0 to 3 where 3 is the negative extreme. Baseline (Day -1) scores were subtracted from Day 28 scores to obtain score change from baseline.
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change From Baseline in Pittsburgh Sleep Quality Index at Day 28 | 0.3 Units on a scale | Standard Deviation 1.1 |
| Low Dose | Change From Baseline in Pittsburgh Sleep Quality Index at Day 28 | 0.3 Units on a scale | Standard Deviation 1.7 |
| Placebo | Change From Baseline in Pittsburgh Sleep Quality Index at Day 28 | 0.7 Units on a scale | Standard Deviation 1.8 |
Secondary
Plasma Concentration
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Plasma Concentration | 4670 ng/mL | Standard Deviation 1470 |
| Low Dose | Plasma Concentration | 2300 ng/mL | Standard Deviation 618 |
| Placebo | Plasma Concentration | 0 ng/mL | Standard Deviation 0 |