Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease (NCT NCT02519036)

NCT ID: NCT02519036

Last Updated: 2019-05-31

Results Overview

An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of Study Drug and subsequently worsened or was not present prior to receiving the first dose of Study Drug but subsequently appeared.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Up to approximately 28 weeks
• Results posted on: 2019-05-31

Participant Flow

46 participants were enrolled in the United Kingdom, Canada and Germany.

Participant milestones

Measure	Placebo Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Overall Study STARTED	12	3	6	6	9	10
Overall Study COMPLETED	12	3	6	6	9	10
Overall Study NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 443139 in Participants With Early Manifest Huntington's Disease

Baseline characteristics by cohort

Measure	Placebo n=12 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 Participants Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	Total n=46 Participants Total of all reporting groups
Age, Continuous	49 years STANDARD_DEVIATION 10 • n=5 Participants	44 years STANDARD_DEVIATION 17 • n=7 Participants	53 years STANDARD_DEVIATION 7 • n=5 Participants	43 years STANDARD_DEVIATION 11 • n=4 Participants	46 years STANDARD_DEVIATION 10 • n=21 Participants	45 years STANDARD_DEVIATION 10 • n=8 Participants	47 years STANDARD_DEVIATION 10 • n=8 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	6 Participants n=8 Participants	18 Participants n=8 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants	4 Participants n=8 Participants	28 Participants n=8 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	9 Participants n=21 Participants	9 Participants n=8 Participants	43 Participants n=8 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized Other Race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	12 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	9 Participants n=21 Participants	10 Participants n=8 Participants	46 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to approximately 28 weeks

Population: Safety set included all participants who were randomized and received at least one dose of study drug.

An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of Study Drug and subsequently worsened or was not present prior to receiving the first dose of Study Drug but subsequently appeared.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 Participants Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Number of Participants With Treatment-related Adverse Events (TEAEs)	12 Participants	3 Participants	6 Participants	6 Participants	9 Participants	9 Participants

SECONDARY outcome

Timeframe: Days 1, 29, 57, 85, and 113 or 141

Population: Pharmacokinetic (PK) population included all participants who were randomized to ISIS 443139, received at least one dose and had sufficient sampling to permit PK evaluation.

Outcome measures

Measure	Placebo n=3 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=6 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=9 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=10 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139 Day 1	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	—
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139 Day 29	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	1.77 nanograms per milliliter (ng/mL) Standard Deviation 1.61	1.55 nanograms per milliliter (ng/mL) Standard Deviation 1.06	2.06 nanograms per milliliter (ng/mL) Standard Deviation 1.01	—
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139 Day 57	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	1.69 nanograms per milliliter (ng/mL) Standard Deviation 0.530	2.77 nanograms per milliliter (ng/mL) Standard Deviation 2.04	2.36 nanograms per milliliter (ng/mL) Standard Deviation 1.34	2.40 nanograms per milliliter (ng/mL) Standard Deviation 1.24	—
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139 Day 85	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	1.96 nanograms per milliliter (ng/mL) Standard Deviation 1.22	2.88 nanograms per milliliter (ng/mL) Standard Deviation 2.54	2.05 nanograms per milliliter (ng/mL) Standard Deviation 1.25	2.53 nanograms per milliliter (ng/mL) Standard Deviation 0.628	—
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139 Day 113	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	1.63 nanograms per milliliter (ng/mL) Standard Deviation 0.250	1.84 nanograms per milliliter (ng/mL) Standard Deviation 1.71	2.28 nanograms per milliliter (ng/mL) Standard Deviation 0.438	2.70 nanograms per milliliter (ng/mL) Standard Deviation 1.20	—
Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139 Day 141	—	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	NA nanograms per milliliter (ng/mL) Standard Deviation NA 'NA' signifies that the values were below the lower limit of quantitation.	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 1 and 85

Population: PK population included all participants who were randomized to ISIS 443139, received at least one dose and had sufficient sampling to permit PK evaluation.

Outcome measures

Measure	Placebo n=3 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=6 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=9 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=10 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Maximum Plasma Concentration (Cmax) for ISIS 443139 Day 1	74.0 ng/mL Geometric Coefficient of Variation 24.3	203 ng/mL Geometric Coefficient of Variation 81.9	500 ng/mL Geometric Coefficient of Variation 39.0	600 ng/mL Geometric Coefficient of Variation 94.9	717 ng/mL Geometric Coefficient of Variation 69.2	—
Maximum Plasma Concentration (Cmax) for ISIS 443139 Day 85	124 ng/mL Geometric Coefficient of Variation 73.6	179 ng/mL Geometric Coefficient of Variation 55.1	396 ng/mL Geometric Coefficient of Variation 77.2	439 ng/mL Geometric Coefficient of Variation 86.0	731 ng/mL Geometric Coefficient of Variation 90.6	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 1 and 85

Population: PK population included all participants who were randomized to ISIS 443139, received at least one dose and had sufficient sampling to permit PK evaluation.

Outcome measures

Measure	Placebo n=3 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=6 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=9 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=10 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Time to Maximum Plasma Concentration (Tmax) for ISIS 443139 Day 1	3.03 hour (h) Interval 2.05 to 5.95	3.03 hour (h) Interval 2.0 to 4.0	1.99 hour (h) Interval 0.533 to 3.08	3.05 hour (h) Interval 2.0 to 8.02	4.00 hour (h) Interval 2.0 to 23.8	—
Time to Maximum Plasma Concentration (Tmax) for ISIS 443139 Day 85	2.02 hour (h) Interval 0.717 to 3.02	2.03 hour (h) Interval 0.55 to 3.07	2.02 hour (h) Interval 1.0 to 4.02	3.02 hour (h) Interval 0.6 to 5.02	4.03 hour (h) Interval 2.0 to 23.9	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Final Assessment (Day 85 or 113)

Population: Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.

Baseline was defined as the last non-missing measure prior to the first dose.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 Participants Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration Baseline	109.13 ng/mL Standard Deviation 42.57	143.65 ng/mL Standard Deviation 49.74	119.83 ng/mL Standard Deviation 45.27	116.70 ng/mL Standard Deviation 30.46	104.99 ng/mL Standard Deviation 65.01	95.87 ng/mL Standard Deviation 35.11
Change From Baseline in CSF Mutant Huntingtin (fM) Protein Concentration Change from Baseline	4.08 ng/mL Standard Deviation 28.47	-31.28 ng/mL Standard Deviation 25.71	-31.98 ng/mL Standard Deviation 24.96	-30.83 ng/mL Standard Deviation 17.17	-45.76 ng/mL Standard Deviation 27.65	-38.41 ng/mL Standard Deviation 21.59

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Final Assessment (Day 85 or 113)

Population: Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.

Baseline was defined as the last non-missing measure prior to the first dose.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 Participants Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Change From Baseline in CSF Neurofilament Light Chain Concentration Baseline	2774 nanograms per liter (ng/L) Standard Deviation 767	2697 nanograms per liter (ng/L) Standard Deviation 1909	2548 nanograms per liter (ng/L) Standard Deviation 916	2280 nanograms per liter (ng/L) Standard Deviation 976	2328 nanograms per liter (ng/L) Standard Deviation 951	2551 nanograms per liter (ng/L) Standard Deviation 872
Change From Baseline in CSF Neurofilament Light Chain Concentration Change from Baseline	324 nanograms per liter (ng/L) Standard Deviation 371	77 nanograms per liter (ng/L) Standard Deviation 223	202 nanograms per liter (ng/L) Standard Deviation 493	274 nanograms per liter (ng/L) Standard Deviation 301	1161 nanograms per liter (ng/L) Standard Deviation 2980	628 nanograms per liter (ng/L) Standard Deviation 1128

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, Days 113, and 197

Population: Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 Participants Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI) Screening	35.58 mL Standard Deviation 19.02	17.88 mL Standard Deviation 12.20	33.02 mL Standard Deviation 17.46	31.90 mL Standard Deviation 13.21	39.33 mL Standard Deviation 23.52	27.53 mL Standard Deviation 19.31
Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI) Day 113	36.11 mL Standard Deviation 19.37	18.66 mL Standard Deviation 12.84	33.56 mL Standard Deviation 17.87	32.04 mL Standard Deviation 14.26	42.24 mL Standard Deviation 25.80	30.36 mL Standard Deviation 21.80
Ventricular Volume as Assessed by Structural Magnetic Resonance Imaging (MRI) Day 197	36.46 mL Standard Deviation 18.97	19.69 mL Standard Deviation 13.03	34.82 mL Standard Deviation 18.16	34.57 mL Standard Deviation 14.82	44.43 mL Standard Deviation 27.37	33.02 mL Standard Deviation 24.61

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Days 84, 141, and 197

Population: Per protocol set included all participants who were randomized and received all doses of the protocol-specified study drug.

The HD Cognitive Battery was developed as a means of measuring cognitive dysfunction in late premanifest and early manifest HD patients. The 6 tests that comprise the battery were selected based on test sensitivity, practice effects, reliability, domain coverage, feasibility for use in clinical trials, and tolerability. A composite cognitive score was calculated by the average z-score of the 6 individual tests. A positive change from baseline indicated improvement in cognitive function; a negative change indicated worsening. Baseline was defined as the last non-missing measure prior to the first dose.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 Participants Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 Participants Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 Participants Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 Participants Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 Participants Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Huntington's Disease (HD) Cognitive Assessment Battery Composite Score Baseline	-0.0860 score on a scale Standard Deviation 0.2941	0.2979 score on a scale Standard Deviation 0.5157	0.0839 score on a scale Standard Deviation 0.5108	-0.0404 score on a scale Standard Deviation 0.3976	-0.1483 score on a scale Standard Deviation 0.3284	0.1212 score on a scale Standard Deviation 0.3877
Huntington's Disease (HD) Cognitive Assessment Battery Composite Score Change at Day 84	-0.0403 score on a scale Standard Deviation 0.2261	0.1314 score on a scale Standard Deviation 0.3670	-0.0430 score on a scale Standard Deviation 0.3585	-0.0338 score on a scale Standard Deviation 0.2756	0.1297 score on a scale Standard Deviation 0.2560	-0.0920 score on a scale Standard Deviation 0.1668
Huntington's Disease (HD) Cognitive Assessment Battery Composite Score Change at Day 141	0.0432 score on a scale Standard Deviation 0.1829	0.4441 score on a scale Standard Deviation 0.8487	-0.1065 score on a scale Standard Deviation 0.2112	-0.1792 score on a scale Standard Deviation 0.2298	0.2194 score on a scale Standard Deviation 0.2224	-0.0547 score on a scale Standard Deviation 0.2136
Huntington's Disease (HD) Cognitive Assessment Battery Composite Score Change at Day 197	-0.0778 score on a scale Standard Deviation 0.2881	0.4202 score on a scale Standard Deviation 1.0482	-0.0469 score on a scale Standard Deviation 0.3151	-0.1633 score on a scale Standard Deviation 0.1170	0.0827 score on a scale Standard Deviation 0.2897	-0.1387 score on a scale Standard Deviation 0.2717

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

ISIS 443139 10 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

ISIS 443139 30 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

ISIS 443139 60 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

ISIS 443139 90 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

ISIS 443139 120 mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=12 participants at risk Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 participants at risk Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 participants at risk Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 participants at risk Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 participants at risk Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 participants at risk Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.

Other adverse events

Measure	Placebo n=12 participants at risk Participants received placebo, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 10 mg n=3 participants at risk Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 30 mg n=6 participants at risk Participants received ISIS 443139, 30 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 60 mg n=6 participants at risk Participants received ISIS 443139, 60 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 90 mg n=9 participants at risk Participants received ISIS 443139, 90 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.	ISIS 443139 120 mg n=10 participants at risk Participants received ISIS 443139, 120 mg, by intrathecal injection, at 4 week intervals over the course of a 13 week treatment period.
Injury, poisoning and procedural complications Procedural pain	50.0% 6/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 1/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	50.0% 3/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	66.7% 6/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	80.0% 8/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	33.3% 4/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 1/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 3/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	50.0% 5/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	25.0% 3/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	22.2% 2/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	20.0% 2/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Skin abrasion	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	22.2% 2/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	20.0% 2/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	16.7% 2/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Joint injury	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Laceration	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Head injury	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Muscle injury	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Tooth injury	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Injury, poisoning and procedural complications Upper limb fracture	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Nasopharyngitis	16.7% 2/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 1/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 3/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	20.0% 2/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	50.0% 3/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Rhinitis	16.7% 2/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	22.2% 2/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Bronchitis	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Influenza	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Rhinovirus infection	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	66.7% 2/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Sinusitis	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Bronchopneumonia	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Conjunctivitis	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Gastrointestinal infection	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Respiratory tract infection	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Viral infection	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Vulvovaginal candidiasis	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Headache	50.0% 6/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	30.0% 3/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Hypoaesthesia	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Paraesthesia	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Tension headache	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Head discomfort	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Pleocytosis	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Nervous system disorders Syncope	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 2/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	22.2% 2/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Coccydynia	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
General disorders Fatigue	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	20.0% 2/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
General disorders Asthenia	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
General disorders Chills	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
General disorders Discomfort	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
General disorders Malaise	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
General disorders Peripheral swelling	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Toothache	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Dental caries	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry skin	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Scab	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin reaction	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Investigations Blood creatine phosphokinase increased	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Investigations Blood thyroid stimulating hormone increased	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Investigations Body temperature increased	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Investigations C-reactive protein increased	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Investigations Thyroxine increased	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Investigations Urine analysis abnormal	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Throat irritation	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Psychiatric disorders Anxiety	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Psychiatric disorders Insomnia	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	10.0% 1/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Psychiatric disorders Mood altered	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Vascular disorders Haematoma	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	33.3% 2/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Bundle branch block right	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Cardiac disorders Ventricular extrasystoles	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Eye disorders Ocular discomfort	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Eye disorders Vision blurred	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	11.1% 1/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Blood and lymphatic system disorders Lymphadenopathy	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Ear and labyrinth disorders Ear pain	8.3% 1/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/12 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/3 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	16.7% 1/6 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/9 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.	0.00% 0/10 • Up to approximately 28 weeks Safety set included all participants who were randomized and received at least one dose of study drug.

Additional Information

Ionis Pharmaceuticals, Inc.

Ionis Pharmaceuticals, Inc.

Phone: 800-679-4747

Email: patients@ionisph.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place