Trial Outcomes & Findings for A Study to Investigate the Long-term Safety and Efficacy of Tolvaptan in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Trial 156-04-251 in Japan] (NCT NCT01280721)
NCT ID: NCT01280721
Last Updated: 2019-01-17
Results Overview
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period. Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
135 participants
Primary outcome timeframe
Baseline, Month12, Month24, and Month36
Results posted on
2019-01-17
Participant Flow
Participant milestones
| Measure |
Tolvaptan
Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg
|
|---|---|
|
Overall Study
STARTED
|
135
|
|
Overall Study
COMPLETED
|
113
|
|
Overall Study
NOT COMPLETED
|
22
|
Reasons for withdrawal
| Measure |
Tolvaptan
Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Physician Decision
|
3
|
|
Overall Study
Withdrawal by Subject
|
6
|
|
Overall Study
eGFR under the withdrawal criteria
|
7
|
|
Overall Study
No tolerability for the lowest dose
|
2
|
Baseline Characteristics
A Study to Investigate the Long-term Safety and Efficacy of Tolvaptan in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Trial 156-04-251 in Japan]
Baseline characteristics by cohort
| Measure |
Tolvaptan
n=135 Participants
Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
135 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
42.7 years
STANDARD_DEVIATION 5.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
77 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
58 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
135 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Month12, Month24, and Month36Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period. Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded.
Outcome measures
| Measure |
Baseline
n=135 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 12
n=123 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 24
n=120 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 36
n=27 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
|---|---|---|---|---|
|
Total Kidney Volume
|
1812.38 mL
Standard Deviation 859.21
|
1878.82 mL
Standard Deviation 950.60
|
1934.14 mL
Standard Deviation 926.79
|
2214.28 mL
Standard Deviation 842.87
|
PRIMARY outcome
Timeframe: Baseline, Month12, Month24, and Month36Estimated glomerular filtration rate calculated by Japanese equation for eGFR during trial period. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded.
Outcome measures
| Measure |
Baseline
n=108 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 12
n=100 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 24
n=99 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 36
n=22 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
|---|---|---|---|---|
|
Renal Function Test (eGFR)
|
61.2 mL/min/1.73 m2
Standard Deviation 21.7
|
56.3 mL/min/1.73 m2
Standard Deviation 21.7
|
51.8 mL/min/1.73 m2
Standard Deviation 20.1
|
43.5 mL/min/1.73 m2
Standard Deviation 20.3
|
PRIMARY outcome
Timeframe: Baseline, Month 12, Month 24, and Month 36Measured values of serum cystatin C concentration during trial period. Number of participants analyzed at each time point represents number of participants with data at the specified time point. Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.) are excluded.
Outcome measures
| Measure |
Baseline
n=108 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 12
n=100 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 24
n=99 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
Month 36
n=22 Participants
Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period
|
|---|---|---|---|---|
|
Renal Function Test (Cys-C)
|
1.016 mg/L
Standard Deviation 0.421
|
1.114 mg/L
Standard Deviation 0.477
|
1.129 mg/L
Standard Deviation 0.466
|
1.281 mg/L
Standard Deviation 0.461
|
Adverse Events
Tolvaptan
Serious events: 20 serious events
Other events: 134 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tolvaptan
n=135 participants at risk
Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg
|
|---|---|
|
Cardiac disorders
Cardiac failure acute
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Cardiac disorders
Angina pectoris
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Ileus
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Umbilical hernias
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Appendicitis
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Sepsis
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Renal cyst infection
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Hepatic cyst infection
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Nasopharyngitis
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Injury, poisoning and procedural complications
Spinal column injury
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Injury, poisoning and procedural complications
Joint dislocations
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute monocytic leukaemia
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine cancer
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Dizziness
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Intracranial aneurysm
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Pregnancy, puerperium and perinatal conditions
Gestational hypertension
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Renal pain
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Renal cyst haemorrhage
|
1.5%
2/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Renal cyst ruptured
|
0.74%
1/135 • Through study completion, 2 to 3 years for major patients
|
Other adverse events
| Measure |
Tolvaptan
n=135 participants at risk
Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg
|
|---|---|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Cardiac disorders
Palpitations
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Cardiac disorders
Tachycardia
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Cardiac disorders
Ventricular extrasystoles
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Congenital, familial and genetic disorders
Congenital cystic kidney disease
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Ear and labyrinth disorders
Vertigo
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Eye disorders
Conjunctival haemorrhage
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Eye disorders
Dry eye
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Eye disorders
Glaucoma
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.9%
8/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Abdominal pain
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Abdominal pain lower
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Constipation
|
5.2%
7/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Dental caries
|
7.4%
10/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Diarrhoea
|
15.6%
21/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Enterocolitis
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Gastritis
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Nausea
|
8.1%
11/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Stomatitis
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Gastrointestinal disorders
Vomiting
|
7.4%
10/135 • Through study completion, 2 to 3 years for major patients
|
|
General disorders
Chest pain
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
General disorders
Malaise
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
General disorders
Oedema peripheral
|
5.9%
8/135 • Through study completion, 2 to 3 years for major patients
|
|
General disorders
Pyrexia
|
5.9%
8/135 • Through study completion, 2 to 3 years for major patients
|
|
General disorders
Thirst
|
77.0%
104/135 • Through study completion, 2 to 3 years for major patients
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
10.4%
14/135 • Through study completion, 2 to 3 years for major patients
|
|
Hepatobiliary disorders
Hepatic steatosis
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Immune system disorders
Seasonal allergy
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Conjunctivitis
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Gastroenteritis
|
9.6%
13/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Hordeolum
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Influenza
|
14.8%
20/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Nasopharyngitis
|
69.6%
94/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Pharyngitis
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Sinusitis
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Viral infection
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Renal cyst infection
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Infections and infestations
Oral herpes
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Injury, poisoning and procedural complications
Contusion
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Investigations
Blood creatine phosphokinase increased
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Investigations
Blood creatinine increased
|
8.9%
12/135 • Through study completion, 2 to 3 years for major patients
|
|
Investigations
Blood pressure increased
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Investigations
Weight decreased
|
5.9%
8/135 • Through study completion, 2 to 3 years for major patients
|
|
Investigations
Weight increased
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Investigations
Hepatic enzyme increased
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
21.5%
29/135 • Through study completion, 2 to 3 years for major patients
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
22.2%
30/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Dizziness
|
7.4%
10/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Dizziness postural
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Dysgeusia
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Headache
|
19.3%
26/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Hypoaesthesia
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Nervous system disorders
Intracranial aneurysm
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Psychiatric disorders
Depression
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Psychiatric disorders
Insomnia
|
5.9%
8/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Dysuria
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Haematuria
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Nocturia
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Pollakiuria
|
57.0%
77/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Polyuria
|
38.5%
52/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Renal cyst haemorrhage
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Renal and urinary disorders
Renal impairment
|
7.4%
10/135 • Through study completion, 2 to 3 years for major patients
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
15.6%
21/135 • Through study completion, 2 to 3 years for major patients
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.2%
3/135 • Through study completion, 2 to 3 years for major patients
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.2%
7/135 • Through study completion, 2 to 3 years for major patients
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.0%
4/135 • Through study completion, 2 to 3 years for major patients
|
|
Skin and subcutaneous tissue disorders
Rash
|
4.4%
6/135 • Through study completion, 2 to 3 years for major patients
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
|
Vascular disorders
Hypertension
|
14.8%
20/135 • Through study completion, 2 to 3 years for major patients
|
|
Vascular disorders
Hypotension
|
3.7%
5/135 • Through study completion, 2 to 3 years for major patients
|
Additional Information
Director of Clinical Trials
Otsuka Pharmaceutical Co., LTD.
Phone: +81-3-6361-7366
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place