Phenylketonuria (PKU)
Conditions
Keywords
PKU, PEG-PAL, Prism, BioMarin, rAvPAL-PEG, BMN165
Brief summary
The BMN 165 clinical development program has been designed to demonstrate the safety and efficacy of BMN 165 in reducing blood Phe concentrations in adults with PKU.
Detailed description
165-302 is a Phase 3, 4 Part, Randomized, Double-Blind, Placebo-Controlled, Discontinuation Study to Evaluate the Efficacy and Safety of Self Administered Subcutaneous Injections of BMN 165 by Adults With PKU. This study is open only to adults who have been exposed to BMN165 in a previous study. Study BMN 165-302 is a four-Part, Phase 3 study. * Part 1: Open-label period * Part 2: A Randomized, double-blind, placebo-controlled period of 8 weeks * Part 3: Two sub-Parts to Part 3:- Part 3A - BMN 165 administered using vial and syringe during this open label period. Part 3B - BMN 165 administered using prefilled syringe during this open-label period. * Part 4: A long-term, open-label extension period.
Interventions
DRUGBMN165 20mg/day
BMN165 20mg/day self-administered daily
DRUGBMN165 40mg/day
BMN165 40mg/day self-administered daily
DRUGPlacebo
Non-drug placebo, self-administered daily
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Individuals eligible to participate in this study must meet all of the following criteria: * Have completed a prior BMN 165 study (PAL-003, 165-205, or 165-301) prior to screening * Have had a stable BMN 165 dose regimen for at least 14 days prior to screening * Are at least 18 y/o and no older than 70 y/o at screening * Subjects who are \< 18 y/o and are already enrolled into Study 165-301 under Amendment #1 (10JAN2014) may enroll into this study * Has identified a person who is \> 18 y/o who has the neurocognitive and linguistic capacities to comprehend and complete the Profile of Mood States (POMS)-Observer rated scale * Has identified a competent person(s) \> 18 y/o who can observe the subject during study drug administration at certain points in the study * A home healthcare nurse may perform the study drug observations * Are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures; for minors, parent or guardian provides written consent and assent may be requested * Are willing and able to comply with all study procedures * For females of childbearing potential, a negative pregnancy test at screening and willing to have additional pregnancy tests during the study * If sexually active, willing to use two acceptable methods of contraception during and for 4 weeks after the study * Males post vasectomy for 2 years with no known pregnancies do not need to use any other forms of contraception during the study. * Females who have been in menopause for at least 2 years, have had a tubal ligation at least 1 year prior to screening, or have had a total hysterectomy do not need to use any other forms of contraception during the study. * Have received documented approval from a study dietitian confirming that the subject is capable of maintaining their diet * Have neurocognitive and linguistic capacities to comprehend and answer investigator's prompts for the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) Investigator rated instrument and to complete the POMS-Subject rated scale * If applicable, maintained stable dose of medication for Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety, or other psychiatric disorder ≥8 weeks prior to enrollment and willing to maintain stable dose throughout study unless a change is medically indicated * General good health, as evidenced by physical examination, clinical laboratory evaluations, and ECG tests at screening
Exclusion criteria
Individuals who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | At Part 2 baseline and change from baseline at Part 2 week 8 | Blood phe concentration in subjects previously exposed to BMN165 who were administered BMN165 20 or 40 mg/day compared with those who were administered a matching placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | At Part 2 baseline and change from baseline at Part 2 week 8 | Attention deficit hyperactivity disorder rating scale IV (ADHD RS-IV) is investigator-rated, 9-item, inattention subscale score ranges from 0 to 27, with higher scores indicative of a greater degree of impairment and a baseline score \>9 indicative of a presence of symptoms. |
| Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | At Part 4 week 57, 105, 161, 209 and 249 | The long term effect of multiple dose levels of BMN165 on blood phe concentration in subjects who are administered BMN165 using pre-filled syringes. |
| Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | At Part 2 baseline and change from baseline at Part 2 week 8 | Phenylketonuria (PKU) Total Mood Disturbance (TMD) Profile of Mood States (POMS) PKU POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely). |
| Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | At Part 2 baseline and change from baseline at Part 2 week 8 | PKU POMS confusion mood domain (referred to as the confusion subscale) is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely). |
| Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | At Part 2 baseline and change from baseline at Part 2 week 8 | Full-length POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely). |
Countries
United States
Participant flow
Recruitment details
This was a multicenter study, conducted in 29 study centers of United States.
Pre-assignment details
A total of 51 out of 215 subjects entered Part 4 directly from 165-301, as they did not receive target dose of 20 or 40 mg/day in 165-301.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects BMN165 20mg/Day:
BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A.
BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B.
Placebo 20mg/Day:
Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2.
BMN165 40mg/Day:
BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A.
BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B.
Placebo 40mg/Day:
Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2.
BMN165:
Up to 60mg/day BMN165 subcutaneous injection administered using a prefilled syringe in Part 4. | 215 |
| Total | 215 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Part 1 (Up to 13 Weeks) | Adverse Event | 4 | 0 | 0 | 0 | 0 |
| Part 1 (Up to 13 Weeks) | Lost to Follow-up | 4 | 0 | 0 | 0 | 0 |
| Part 1 (Up to 13 Weeks) | Physician Decision | 2 | 0 | 0 | 0 | 0 |
| Part 1 (Up to 13 Weeks) | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 |
| Part 2 (8 Weeks) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
| Part 4 (Up to 274 Weeks) | Adverse Event | 0 | 0 | 0 | 0 | 5 |
| Part 4 (Up to 274 Weeks) | Lost to Follow-up | 0 | 0 | 0 | 0 | 4 |
| Part 4 (Up to 274 Weeks) | Physician Decision | 0 | 0 | 0 | 0 | 5 |
| Part 4 (Up to 274 Weeks) | Protocol deviations | 0 | 0 | 0 | 0 | 2 |
| Part 4 (Up to 274 Weeks) | Subject withdrew consent | 0 | 0 | 0 | 0 | 14 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 29.22 yrs STANDARD_DEVIATION 8.74 |
| Age, Customized 16 - <18 years | 11 Participants |
| Age, Customized 18 - <66 years | 204 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Black/African American | 2 Participants |
| Race/Ethnicity, Customized White | 211 Participants |
| Sex: Female, Male Female | 105 Participants |
| Sex: Female, Male Male | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 78 | 0 / 34 | 0 / 32 | 0 / 15 | 0 / 14 | 0 / 23 | 0 / 18 | 0 / 11 | 0 / 8 | 0 / 67 | 0 / 152 | 0 / 186 | 0 / 89 |
| other Total, other adverse events | 70 / 86 | 59 / 78 | 27 / 34 | 28 / 32 | 14 / 15 | 13 / 14 | 19 / 23 | 15 / 18 | 8 / 11 | 7 / 8 | 62 / 67 | 105 / 152 | 178 / 186 | 59 / 89 |
| serious Total, serious adverse events | 6 / 86 | 2 / 78 | 0 / 34 | 2 / 32 | 1 / 15 | 0 / 14 | 1 / 23 | 0 / 18 | 0 / 11 | 0 / 8 | 7 / 67 | 6 / 152 | 16 / 186 | 5 / 89 |
Outcome results
Primary
Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2
Blood phe concentration in subjects previously exposed to BMN165 who were administered BMN165 20 or 40 mg/day compared with those who were administered a matching placebo.
Time frame: At Part 2 baseline and change from baseline at Part 2 week 8
Population: Modified Intent-to-Treat (mITT) population consists of all subjects who reached the randomized dose of 20mg/day or 40mg/day and were randomized into Part 2 with a mean blood Phe reduction of ≥20% (using the last two consecutive blood Phe assessments of Part 1) from the baseline of 165-301 (or the Phase 2 study in which they initiated BMN165).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN165 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Part 2 Baseline | 596.8 µmol/L | Standard Deviation 582.75 |
| BMN165 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Change from Baseline Part 2 Week 8 | -65.9 µmol/L | Standard Deviation 192.02 |
| Placebo 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Change from Baseline Part 2 Week 8 | 996.4 µmol/L | Standard Deviation 555 |
| Placebo 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Part 2 Baseline | 563.9 µmol/L | Standard Deviation 504.62 |
| BMN165 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Part 2 Baseline | 410.9 µmol/L | Standard Deviation 439.95 |
| BMN165 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Change from Baseline Part 2 Week 8 | 114.1 µmol/L | Standard Deviation 332.4 |
| Placebo 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Part 2 Baseline | 508.2 µmol/L | Standard Deviation 363.68 |
| Placebo 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 | Change from Baseline Part 2 Week 8 | 599.0 µmol/L | Standard Deviation 507.4 |
Comparison: Change in blood Phe concentration during Part 2 in subjects previously exposed to BMN165 who self administer BMN165 20mg/day compared with those who self administer matching placebo.p-value: <0.000195% CI: [-1204.19, -741.85]ANCOVA
Comparison: Change in blood Phe concentration during Part 2 in subjects previously exposed to BMN165 who self administer BMN165 40mg/day compared with those who self administer matching placebo.p-value: <0.000195% CI: [-830.07, -346.94]ANCOVA
Secondary
Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4
The long term effect of multiple dose levels of BMN165 on blood phe concentration in subjects who are administered BMN165 using pre-filled syringes.
Time frame: At Part 4 week 57, 105, 161, 209 and 249
Population: All Subjects Entered 165-302 Part 4 Data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN165 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 105 | -1015.3 µmol/L | Standard Deviation 557 |
| BMN165 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 249 | -1059.5 µmol/L | Standard Deviation 160.51 |
| BMN165 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 161 | -1006.5 µmol/L | Standard Deviation 514.76 |
| BMN165 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 209 | -897.3 µmol/L | Standard Deviation 494.41 |
| BMN165 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 57 | -1004.9 µmol/L | Standard Deviation 541.19 |
| Placebo 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 161 | -1111.9 µmol/L | Standard Deviation 519.4 |
| Placebo 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 57 | -984.0 µmol/L | Standard Deviation 531.33 |
| Placebo 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 105 | -1109.2 µmol/L | Standard Deviation 474.25 |
| Placebo 20mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 209 | -1020.4 µmol/L | Standard Deviation 495.79 |
| BMN165 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 105 | -858.5 µmol/L | Standard Deviation 593.73 |
| BMN165 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 57 | -810.2 µmol/L | Standard Deviation 595.24 |
| BMN165 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 161 | -662.8 µmol/L | Standard Deviation 433.8 |
| BMN165 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 209 | -541.6 µmol/L | Standard Deviation 245.83 |
| Placebo 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 57 | -662.3 µmol/L | Standard Deviation 465.61 |
| Placebo 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 105 | -641.0 µmol/L | Standard Deviation 568.67 |
| Placebo 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 161 | -808.6 µmol/L | Standard Deviation 558.22 |
| Placebo 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 249 | -1314.0 µmol/L | — |
| Placebo 40mg/Day | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 209 | -961.7 µmol/L | Standard Deviation 339.92 |
| BMN165 All Dose - Part 4 | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 249 | -1144.3 µmol/L | Standard Deviation 185.67 |
| BMN165 All Dose - Part 4 | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 57 | -839.5 µmol/L | Standard Deviation 562.74 |
| BMN165 All Dose - Part 4 | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 161 | -882.0 µmol/L | Standard Deviation 528.61 |
| BMN165 All Dose - Part 4 | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 105 | -890.8 µmol/L | Standard Deviation 578.38 |
| BMN165 All Dose - Part 4 | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 | Change from Baseline to Part 4 Week 209 | -842.3 µmol/L | Standard Deviation 418.37 |
Secondary
Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2
Attention deficit hyperactivity disorder rating scale IV (ADHD RS-IV) is investigator-rated, 9-item, inattention subscale score ranges from 0 to 27, with higher scores indicative of a greater degree of impairment and a baseline score \>9 indicative of a presence of symptoms.
Time frame: At Part 2 baseline and change from baseline at Part 2 week 8
Population: mITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Baseline | 5.9 Units on a scale | Standard Deviation 4.7 |
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Change from Baseline Part 2 Week 8 | 1.1 Units on a scale | Standard Deviation 3.96 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Change from Baseline Part 2 Week 8 | 1.2 Units on a scale | Standard Deviation 3 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Baseline | 5.0 Units on a scale | Standard Deviation 4.26 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Baseline | 6.0 Units on a scale | Standard Deviation 6.45 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Change from Baseline Part 2 Week 8 | 0.5 Units on a scale | Standard Deviation 5.36 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Baseline | 2.9 Units on a scale | Standard Deviation 3.68 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 | Change from Baseline Part 2 Week 8 | -0.4 Units on a scale | Standard Deviation 3.44 |
Secondary
Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2
PKU POMS confusion mood domain (referred to as the confusion subscale) is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).
Time frame: At Part 2 baseline and change from baseline at Part 2 week 8
Population: mITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Baseline | 2.0 Units on a scale | Standard Deviation 2.09 |
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Change from Baseline Part 2 Week 8 | 0.8 Units on a scale | Standard Deviation 2.79 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Change from Baseline Part 2 Week 8 | 1.4 Units on a scale | Standard Deviation 2.47 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Baseline | 2.1 Units on a scale | Standard Deviation 1.49 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Baseline | 2.4 Units on a scale | Standard Deviation 2.02 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Change from Baseline Part 2 Week 8 | -0.3 Units on a scale | Standard Deviation 1.84 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Baseline | 1.2 Units on a scale | Standard Deviation 1.53 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 | Change from Baseline Part 2 Week 8 | 0.5 Units on a scale | Standard Deviation 2.22 |
Secondary
Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2
Phenylketonuria (PKU) Total Mood Disturbance (TMD) Profile of Mood States (POMS) PKU POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).
Time frame: At Part 2 baseline and change from baseline at Part 2 week 8
Population: mITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Baseline | 7.1 Units on a scale | Standard Deviation 14.18 |
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | 4.8 Units on a scale | Standard Deviation 12.63 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | 4.3 Units on a scale | Standard Deviation 11.96 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Baseline | 8.6 Units on a scale | Standard Deviation 10.84 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Baseline | 8.9 Units on a scale | Standard Deviation 12.28 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | -2.0 Units on a scale | Standard Deviation 10.25 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Baseline | 5.0 Units on a scale | Standard Deviation 8.56 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | 0.0 Units on a scale | Standard Deviation 14.08 |
Secondary
Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2
Full-length POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).
Time frame: At Part 2 baseline and change from baseline at Part 2 week 8
Population: mITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Baseline | 16.2 Units on a scale | Standard Deviation 35.63 |
| BMN165 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | 13.1 Units on a scale | Standard Deviation 30.73 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | 7.3 Units on a scale | Standard Deviation 26.23 |
| Placebo 20mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Baseline | 18.1 Units on a scale | Standard Deviation 28.26 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Baseline | 24.3 Units on a scale | Standard Deviation 35.38 |
| BMN165 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | -3.2 Units on a scale | Standard Deviation 26.63 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Baseline | 13.3 Units on a scale | Standard Deviation 21.63 |
| Placebo 40mg/Day | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 | Change from Baseline Part 2 Week 8 | -1.7 Units on a scale | Standard Deviation 29.34 |