Trial Outcomes & Findings for Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands (NCT NCT03548415)

NCT ID: NCT03548415

Last Updated: 2022-11-14

Results Overview

IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Percent change from Baseline in IGF-1 levels was measured at Day 141. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic (PD) activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 43 participants
• Primary outcome timeframe: Baseline and 28 days after last dose (Day 141)
• Results posted on: 2022-11-14

Participant Flow

Participants took part in the study at 24 investigative sites in Lithuania, Hungary, the United States of America, Serbia, Russia, Poland, and Romania from 13 September 2018 to 02 April 2021.

Adult participants diagnosed with acromegaly were randomized into 4 cohorts [Cohorts A and B in 2:1 ratio; Cohorts C and D in 5:1 ratio] to receive IONIS GHR-LRx or placebo. Due to enrollment difficulties associated with (COVID-19) pandemic, treatment groups IONIS GHR-LRx, 120 mg and IONIS GHR-LRx, 160 mg did not complete enrollment resulting in cohort sizes smaller than planned.

Participant milestones

Measure	Placebo Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	Cohort A: IONIS GHR-LRx, 60 mg Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.	Cohort B: IONIS GHR-LRx, 80 mg Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Overall Study STARTED	12	12	11	2	6
Overall Study Per-Protocol Set	12	11	11	2	5
Overall Study COMPLETED	12	11	11	2	5
Overall Study NOT COMPLETED	0	1	0	0	1

Reasons for withdrawal

Measure	Placebo Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	Cohort A: IONIS GHR-LRx, 60 mg Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.	Cohort B: IONIS GHR-LRx, 80 mg Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Overall Study Adverse Event or Serious Adverse Event	0	1	0	0	1

Baseline Characteristics

Safety, Tolerability, and Efficacy of IONIS-GHR-LRx in Participants With Acromegaly Being Treated With Long-acting Somatostatin Receptor Ligands

Baseline characteristics by cohort

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	Cohort A: IONIS GHR-LRx, 60 mg n=12 Participants Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.	Cohort B: IONIS GHR-LRx, 80 mg n=11 Participants Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 Participants Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 Participants Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.	Total n=43 Participants Total of all reporting groups
Age, Continuous	45.3 years STANDARD_DEVIATION 11.7 • n=5 Participants	48.9 years STANDARD_DEVIATION 13.6 • n=7 Participants	52.1 years STANDARD_DEVIATION 14.9 • n=5 Participants	53.5 years STANDARD_DEVIATION 2.1 • n=4 Participants	46.0 years STANDARD_DEVIATION 13.3 • n=21 Participants	48.5 years STANDARD_DEVIATION 12.9 • n=10 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants	27 Participants n=10 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	16 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	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	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants	43 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	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	0 Participants n=10 Participants
Race (NIH/OMB) Asian	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	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	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	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	00 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	12 Participants n=7 Participants	11 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants	42 Participants n=10 Participants
Race (NIH/OMB) More than one 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	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	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	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline and 28 days after last dose (Day 141)

Population: The Per-protocol Set included all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or pharmacodynamic assessment, received at least 5 of the 6 doses of Study Drug with the first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Low dose refers to 60 mg or 80 mg, High dose refers to 120 mg or 160 mg.

IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Percent change from Baseline in IGF-1 levels was measured at Day 141. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic (PD) activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=22 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=7 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Percent Change in Serum Insulin-like Growth Factor-1 (IGF-1) From Baseline to 28 Days After Last Dose	8.9 percent change Standard Deviation 31.5	-2.8 percent change Standard Deviation 33.1	-7.5 percent change Standard Deviation 16.3	—	—

PRIMARY outcome

Timeframe: Up to 211 days

Population: The Safety Set included all participants who were randomized and received at least one dose of Study Drug.

A TEAE was defined as an adverse event that occurred after the initiation of study drug dosing and before the end of the follow-up period.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=12 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=11 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 Participants Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 Participants Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	8 Participants	11 Participants	7 Participants	2 Participants	5 Participants

PRIMARY outcome

Timeframe: Up to 211 days

Population: The Safety Set included all participants who were randomized and received at least one dose of Study Drug.

Vitals signs included blood pressure, heart rate, respiratory rate, and temperature recorded throughout the study. Clinical significance was determined by the investigator.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=12 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=11 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 Participants Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 Participants Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings Hypotension	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings Hypertension	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 211 days

Population: The Safety Set included all participants who were randomized and received at least one dose of Study Drug.

Physical examination included weight and body mass index (BMI) recorded throughout the study. Clinical significance was determined by the investigator.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=12 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=11 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 Participants Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 Participants Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Number of Participants With TEAEs Related to Clinically Significant Physical Examination Findings	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 211 days

Population: The Safety Set included all participants who were randomized and received at least one dose of Study Drug.

Clinical laboratory assessments included clinical chemistry, hematology, and urinalysis. Clinically-significant abnormal laboratory values were reported as TEAEs if the results may, in the opinion of the Investigator, constitute or be associated with an AE.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=12 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=11 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 Participants Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 Participants Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings Hyperglycaemia	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings Blood urine present	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings Mean cell volume increased	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings Urine protein/creatinine ratio increased	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 211 days

Population: The Safety Set included all participants who were randomized and received at least one dose of Study Drug.

ECG assessments included QT, QRS duration, PR interval, ventricular rate, QTcB, QTcF.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=12 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=11 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 Participants Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 Participants Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Number of Participants With TEAEs Related to Clinically Significant Electrocardiogram (ECG) Findings	2 Participants	2 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to 28 days after last dose (Day 141)

Population: The Per-protocol Set included all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or pharmacodynamic assessment, received at least 5 of the 6 doses of Study Drug with the first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Low dose refers to 60 mg or 80 mg, High dose refers to 120 mg or 160 mg.

Normalization of circulating IGF-1 is a validated marker for the treatment of acromegaly. IGF-1 assessments were based on a single serum sample taken in fasting conditions, prior to the study drug administration. Normal IGF-1 levels for a participant differ based on age and gender. Number of participants with a normal IGF-1 level which were 1.2 times within gender and age limits after 28 days of the last dose (Day 141) are presented. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=22 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=7 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Number of Participants Achieving Normalized IGF-1 Levels to Within 1.2 Times of Gender and Age Limits at 28 Days After Last Dose	0 Participants	5 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Baseline to 28 days after last dose (Day 141)

Population: The Per-protocol Set included all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or pharmacodynamic assessment, received at least 5 of the 6 doses of Study Drug with the first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Low dose refers to 60 mg or 80 mg, High dose refers to 120 mg or 160 mg.

Normalization of circulating IGF-1 is a validated marker for the treatment of acromegaly. IGF-1 assessments were based on a single serum sample taken in fasting conditions, prior to the study drug administration. Normal IGF-1 levels for a participant differ based on age and gender. Number of participants with a normal IGF-1 level which were 1.0 times within gender and age limits after 28 days of the last dose (Day 141) are presented. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=22 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=7 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Number of Participants Achieving Normalized IGF-1 Levels to Within 1.0 Times of Gender and Age Limits at 28 Days After Last Dose	0 Participants	2 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 141, 155, 183, and 211

Population: Per-protocol Set:all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or PD assessment, received at least 5 of 6 doses of Study Drug with first 3 doses administered on schedule, and had no significant protocol deviations that would have been expected to affect efficacy. Number analyzed is the number of participants with data available at specific timepoints. Low dose refers to 60 mg or 80 mg,High dose refers to 120 mg or 160 mg.

IGF-1 is a hormone that manages the effects of GH in the body. Change from Baseline in IGF-1 levels was measured at multiple timepoints up to Day 211. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=22 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=7 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 57	52 nanograms per milliliter Standard Deviation 120	-39 nanograms per milliliter Standard Deviation 147	-74 nanograms per milliliter Standard Deviation 63	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 71	9 nanograms per milliliter Standard Deviation 115	-71 nanograms per milliliter Standard Deviation 163	-78 nanograms per milliliter Standard Deviation 76	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 85	9 nanograms per milliliter Standard Deviation 91	-55 nanograms per milliliter Standard Deviation 136	-90 nanograms per milliliter Standard Deviation 141	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 99	13 nanograms per milliliter Standard Deviation 124	-49 nanograms per milliliter Standard Deviation 104	-104 nanograms per milliliter Standard Deviation 78	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 112	31 nanograms per milliliter Standard Deviation 93	-36 nanograms per milliliter Standard Deviation 100	-61 nanograms per milliliter Standard Deviation 70	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 127	19 nanograms per milliliter Standard Deviation 83	-48 nanograms per milliliter Standard Deviation 133	-74 nanograms per milliliter Standard Deviation 69	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 141	20 nanograms per milliliter Standard Deviation 100	-39 nanograms per milliliter Standard Deviation 140	-48 nanograms per milliliter Standard Deviation 92	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 155	1 nanograms per milliliter Standard Deviation 91	-47 nanograms per milliliter Standard Deviation 144	-98 nanograms per milliliter Standard Deviation 112	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 183	-13 nanograms per milliliter Standard Deviation 87	-45 nanograms per milliliter Standard Deviation 155	-15 nanograms per milliliter Standard Deviation 146	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 211	13 nanograms per milliliter Standard Deviation 116	-55 nanograms per milliliter Standard Deviation 161	-92 nanograms per milliliter Standard Deviation 97	—	—
Change From Baseline in Serum IGF-1 Over Time Baseline	386 nanograms per milliliter Standard Deviation 154	422 nanograms per milliliter Standard Deviation 214	419 nanograms per milliliter Standard Deviation 143	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 15	33 nanograms per milliliter Standard Deviation 112	-46 nanograms per milliliter Standard Deviation 108	-10 nanograms per milliliter Standard Deviation 47	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 29	23 nanograms per milliliter Standard Deviation 71	-30 nanograms per milliliter Standard Deviation 140	-68 nanograms per milliliter Standard Deviation 55	—	—
Change From Baseline in Serum IGF-1 Over Time Change from Baseline at Day 43	17 nanograms per milliliter Standard Deviation 114	-41 nanograms per milliliter Standard Deviation 142	-88 nanograms per milliliter Standard Deviation 95	—	—

SECONDARY outcome

Timeframe: Baseline, Days 15, 29, 43, 57, 71, 85, 99, 112, 127, 155, 183, and 211

Population: Per-protocol Set:all randomized participants who received at least one dose of Study Drug and had at least one post-baseline efficacy or PD assessment, received at least 5 of 6 doses of Study Drug with first 3 doses administered on schedule,and had no significant protocol deviations that would have been expected to affect efficacy. Number analyzed is number of participants with data available for analysis at specific timepoint.Low dose refers to 60 mg or 80 mg,High dose refers to 120mg or 160mg.

IGF-1 is a hormone that manages the effects of GH in the body. Percent change from Baseline in IGF-1 levels was measured at multiple timepoints up to Day 211. Baseline was defined as the last non-missing value prior to the first administration of Study Drug (ISIS 766720 or placebo). A negative percent change from Baseline indicated improvement. To perform a meaningful assessment of the pharmacodynamic activity of ISIS 766720, the lower dose groups (60 mg and 80 mg) and higher dose groups (120 mg and 160 mg) were combined to achieve group size of 7 or more for PD assessments and these were designated as low-dose and high-dose groups respectively.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	ISIS 766720 Low Dose n=22 Participants Participants received IONIS GHR-LRx, 60 or 80 milligrams (mg), SC, once every 4 weeks for 16 weeks.	ISIS 766720 High Dose n=7 Participants Participants received IONIS GHR-LRx, 120 or 160 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 71	8.8 percent change Standard Deviation 33.4	-9.0 percent change Standard Deviation 42.0	-16.5 percent change Standard Deviation 12.3	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 85	4.2 percent change Standard Deviation 27.2	-5.6 percent change Standard Deviation 32.5	-16.7 percent change Standard Deviation 19.4	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 99	6.6 percent change Standard Deviation 38.8	-7.1 percent change Standard Deviation 30.1	-25.1 percent change Standard Deviation 18.0	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 112	12.1 percent change Standard Deviation 29.8	-4.0 percent change Standard Deviation 33.6	-12.3 percent change Standard Deviation 9.3	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 127	6.3 percent change Standard Deviation 19.6	-4.7 percent change Standard Deviation 30.2	-16.0 percent change Standard Deviation 9.0	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 141	8.9 percent change Standard Deviation 31.5	-2.8 percent change Standard Deviation 33.1	-7.5 percent change Standard Deviation 16.3	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 155	4.1 percent change Standard Deviation 26.0	-3.5 percent change Standard Deviation 32.0	-18.1 percent change Standard Deviation 14.1	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 183	0.1 percent change Standard Deviation 26.2	-2.5 percent change Standard Deviation 38.7	1.6 percent change Standard Deviation 25.9	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 211	2.2 percent change Standard Deviation 30.6	-8.2 percent change Standard Deviation 32.7	-15.6 percent change Standard Deviation 10.5	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 15	11.2 percent change Standard Deviation 31.3	-6.0 percent change Standard Deviation 24.5	-0.2 percent change Standard Deviation 11.9	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 29	9.3 percent change Standard Deviation 26.2	-3.5 percent change Standard Deviation 30.0	-14.8 percent change Standard Deviation 6.8	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 43	9.6 percent change Standard Deviation 35.7	-5.1 percent change Standard Deviation 28.4	-18.3 percent change Standard Deviation 18.5	—	—
Percent Change From Baseline in Serum IGF-1 Over Time Percent Change from Baseline at Day 57	14.3 percent change Standard Deviation 34.5	-3.4 percent change Standard Deviation 31.9	-16.6 percent change Standard Deviation 11.6	—	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Cohort A: IONIS GHR-LRx, 60 mg

Serious events: 1 serious events

Other events: 11 other events

Deaths: 1 deaths

Cohort B: IONIS GHR-LRx, 80 mg

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort C: IONIS GHR-LRx, 120 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort D: IONIS GHR-LRx, 160 mg

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=12 participants at risk Participants received placebo by subcutaneous injection (SC) once every 4 weeks for 16 weeks.	Cohort A: IONIS GHR-LRx, 60 mg n=12 participants at risk Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.	Cohort B: IONIS GHR-LRx, 80 mg n=11 participants at risk Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 participants at risk Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 participants at risk Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Gastrointestinal disorders Intra-abdominal haemorrhage	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Gastrointestinal bacterial infection	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Pneumonia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Septic shock	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Angina pectoris	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Myocardial infarction	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Metabolism and nutrition disorders Cholecystitis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The 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 subcutaneous injection (SC) once every 4 weeks for 16 weeks.	Cohort A: IONIS GHR-LRx, 60 mg n=12 participants at risk Participants received IONIS GHR-LRx, 60 milligrams (mg), SC, once every 4 weeks for 16 weeks.	Cohort B: IONIS GHR-LRx, 80 mg n=11 participants at risk Participants received IONIS GHR-LRx, 80 mg, SC, once every 4 weeks for 16 weeks.	Cohort C: IONIS GHR-LRx, 120 mg n=2 participants at risk Participants received IONIS GHR-LRx, 120 mg, SC, once every 4 weeks for 16 weeks.	Cohort D: IONIS GHR-LRx, 160 mg n=6 participants at risk Participants received IONIS GHR-LRx, 160 mg, SC, once every 4 weeks for 16 weeks.
Infections and infestations Urinary tract infection	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 2/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	33.3% 2/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 2/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Cervicitis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Enterovirus infection	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Gastrointestinal bacterial infection	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Nasopharyngitis	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Periodontitis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Pharyngitis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Pneumonia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Septic shock	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Infections and infestations Pyelonephritis chronic	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Nausea	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 2/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	18.2% 2/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Constipation	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Intra-abdominal haemorrhage	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Pancreatitis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Abdominal pain upper	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Gastritis	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Gastrointestinal disorders Glossitis	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Blood creatine phosphokinase increased	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	18.2% 2/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Alanine aminotransferase increased	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Aspartate aminotransferase increased	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Bacterial test positive	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Blood urine present	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Mean cell volume increased	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Urine protein/creatinine ratio increased	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Electrocardiogram QRS complex prolonged	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Investigations Heart rate irregular	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Sinus bradycardia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 2/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Angina pectoris	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Bundle branch block	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Coronary artery disease	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Left ventricular hypertrophy	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Myocardial infarction	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Bradycardia	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Palpitations	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Cardiac disorders Supraventricular extrasystoles	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
General disorders Chest pain	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
General disorders Injection site erythema	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	18.2% 2/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
General disorders Injection site inflammation	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
General disorders Pain	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
General disorders Pyrexia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
General disorders Asthenia	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Metabolism and nutrition disorders Glucose tolerance impaired	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Metabolism and nutrition disorders Hyperglycaemia	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Nervous system disorders Headache	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	18.2% 2/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Nervous system disorders Somnolence	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Respiratory, thoracic and mediastinal disorders Snoring	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Vascular disorders Hot flush	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Vascular disorders Hypertension	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Vascular disorders Hypotension	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Vascular disorders Poor peripheral circulation	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Vascular disorders Thrombophlebitis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Injury, poisoning and procedural complications Fall	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Injury, poisoning and procedural complications Limb injury	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The 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 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Injury, poisoning and procedural complications Wound	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Renal and urinary disorders Albuminuria	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Renal and urinary disorders Bladder pain	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Renal and urinary disorders Haematuria	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Renal and urinary disorders Nephrolithiasis	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	9.1% 1/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Renal and urinary disorders Dysuria	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Renal and urinary disorders Renal cyst	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Hepatobiliary disorders Cholecystitis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer stage I	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Blood and lymphatic system disorders Iron deficiency anaemia	16.7% 2/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Congenital, familial and genetic disorders Type V hyperlipidaemia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Endocrine disorders Acromegaly	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Eye disorders Asthenopia	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Psychiatric disorders Depression	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	50.0% 1/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/6 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.
Skin and subcutaneous tissue disorders Acne	8.3% 1/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/12 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/11 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	0.00% 0/2 • Up to 211 days The Safety Set included all participants who were randomized and received at least one dose of Study Drug.	16.7% 1/6 • Up to 211 days The 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