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]
Sponsor
Otsuka Pharmaceutical Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT01280721
Collaborator
(none)
135
7
1
45
19.3
0.4
Study Details
Study Description
Brief Summary
ADPKD patients who enrolled in Trial 156-04-251 will receive repeated oral administration of tolvaptan twice daily (morning and evening: 45mg/15mg, 60mg/30mg, or 90mg/30mg).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
135 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-label Extension 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]
Study Start Date
:
Nov 1, 2010
Actual Primary Completion Date
:
Aug 1, 2014
Actual Study Completion Date
:
Aug 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: tolvaptan Repeated oral administration twice daily (morning and evening) at one of three split dose-regimens 45mg/15mg, 60mg/30mg or 90mg/30mg. |
Drug: tolvaptan
Repeated oral administration twice daily (morning and evening) at one of three split dose-regimens 45mg/15mg, 60mg/30mg or 90mg/30mg.
|
Outcome Measures
Primary Outcome Measures
- Total Kidney Volume [Baseline, Month12, Month24, and Month36]
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 Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.)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.
- Renal Function Test (eGFR) [Baseline, Month12, Month24, and Month36]
Estimated 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 Patients who were withdrawn from trial or have no appropriate data (e.g., interruption of medication, protocol deviation, etc.)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.
- Renal Function Test (Cys-C) [Baseline, Month 12, Month 24, and Month 36]
Measured 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
23 Years
to 53 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients who participated in Trial 156-04-251 in Japan and for whom CRF collection has been completed.
-
Patients who completed 3-year repeated administration and who completed the second follow-up visit or patients whose treatment with the trial drug was interupted due to pregnancy and who completed out the second follow-up visit in Trial 156-04-251.
-
Patients in whom any adverse events occurring in Trial 156-04-251 were resolved orstabilized and require no further follow-up.
Exclusion Criteria:
-
Patients with eGFR of less than 15 mL/min/1.73 m2
-
Pregnant, breast-feeding, or possibly pregnant women or women who are planning to become pregnant
-
Patients who received any investigational drug other than Tolvaptan within 30 days prior to commencement of administration of tolvaptan
-
Any patients who, in the opinion of the principle investigator or subinvestigators, should not participate in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chubu Region | Japan | |||
| 2 | Chugoku Region | Japan | |||
| 3 | Hokkaido Region | Japan | |||
| 4 | Kanto Region | Japan | |||
| 5 | Kinki Region | Japan | |||
| 6 | Kyushu Region | Japan | |||
| 7 | Tohoku Region | Japan |
Sponsors and Collaborators
- Otsuka Pharmaceutical Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01280721
Other Study ID Numbers:
- 156-10-003
- JapicCTI-101362
First Posted:
Jan 21, 2011
Last Update Posted:
Jan 17, 2019
Last Verified:
Aug 1, 2018
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Tolvaptan |
|---|---|
| Arm/Group Description | Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg |
| Period Title: Overall Study | |
| STARTED | 135 |
| COMPLETED | 113 |
| NOT COMPLETED | 22 |
Baseline Characteristics
| Arm/Group Title | Tolvaptan |
|---|---|
| Arm/Group Description | Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg |
| Overall Participants | 135 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
135
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
42.7
(5.9)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
77
57%
|
| Male |
58
43%
|
| Region of Enrollment (participants) [Number] | |
| Japan |
135
100%
|
Outcome Measures
| Title | Total Kidney Volume |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Month12, Month24, and Month36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Baseline | Month 12 | Month 24 | Month 36 |
|---|---|---|---|---|
| Arm/Group Description | Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period | Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period | Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period | Measured values of total kidney volume (sum of the volume of the left and right kidneys) during trial period |
| Measure Participants | 135 | 123 | 120 | 27 |
| Mean (Standard Deviation) [mL] |
1812.38
(859.21)
|
1878.82
(950.60)
|
1934.14
(926.79)
|
2214.28
(842.87)
|
| Title | Renal Function Test (eGFR) |
|---|---|
| Description | Estimated 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. |
| Time Frame | Baseline, Month12, Month24, and Month36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Baseline | Month 12 | Month 24 | Month 36 |
|---|---|---|---|---|
| Arm/Group Description | Estimated glomerular filtration rate calculated by Japanese equation for eGFR during trial period | Estimated glomerular filtration rate calculated by Japanese equation for eGFR during trial period | Estimated glomerular filtration rate calculated by Japanese equation for eGFR during trial period | Estimated glomerular filtration rate calculated by Japanese equation for eGFR during trial period |
| Measure Participants | 108 | 100 | 99 | 22 |
| Mean (Standard Deviation) [mL/min/1.73 m2] |
61.2
(21.7)
|
56.3
(21.7)
|
51.8
(20.1)
|
43.5
(20.3)
|
| Title | Renal Function Test (Cys-C) |
|---|---|
| Description | Measured 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. |
| Time Frame | Baseline, Month 12, Month 24, and Month 36 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Baselime | Month 12 | Month 24 | Month 36 |
|---|---|---|---|---|
| Arm/Group Description | Measured values of serum cystatin C concentration during trial period | Measured values of serum cystatin C concentration during trial period | Measured values of serum cystatin C concentration during trial period | Measured values of serum cystatin C concentration during trial period |
| Measure Participants | 108 | 100 | 99 | 22 |
| Mean (Standard Deviation) [mg/L] |
1.016
(0.421)
|
1.114
(0.477)
|
1.129
(0.466)
|
1.281
(0.461)
|
Adverse Events
| Time Frame | Through study completion, 2 to 3 years for major patients | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Tolvaptan | |
| Arm/Group Description | Twice-daily repeated oral administration of tolvaptan at daily doses of 60 to 120 mg | |
All Cause Mortality |
||
| Tolvaptan | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/135 (0%) | |
Serious Adverse Events |
||
| Tolvaptan | ||
| Affected / at Risk (%) | # Events | |
| Total | 20/135 (14.8%) | |
| Cardiac disorders | ||
| Cardiac failure acute | 1/135 (0.7%) | |
| Angina pectoris | 1/135 (0.7%) | |
| Gastrointestinal disorders | ||
| Ileus | 1/135 (0.7%) | |
| Umbilical hernias | 1/135 (0.7%) | |
| Infections and infestations | ||
| Appendicitis | 1/135 (0.7%) | |
| Sepsis | 1/135 (0.7%) | |
| Renal cyst infection | 4/135 (3%) | |
| Hepatic cyst infection | 1/135 (0.7%) | |
| Nasopharyngitis | 1/135 (0.7%) | |
| Injury, poisoning and procedural complications | ||
| Ligament rupture | 1/135 (0.7%) | |
| Spinal column injury | 1/135 (0.7%) | |
| Hand fracture | 1/135 (0.7%) | |
| Joint dislocations | 1/135 (0.7%) | |
| Musculoskeletal and connective tissue disorders | ||
| Spondylolisthesis | 1/135 (0.7%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Uterine leiomyoma | 1/135 (0.7%) | |
| Acute monocytic leukaemia | 1/135 (0.7%) | |
| Ovarian cancer | 1/135 (0.7%) | |
| Uterine cancer | 1/135 (0.7%) | |
| Nervous system disorders | ||
| Subarachnoid haemorrhage | 1/135 (0.7%) | |
| Dizziness | 1/135 (0.7%) | |
| Intracranial aneurysm | 1/135 (0.7%) | |
| Pregnancy, puerperium and perinatal conditions | ||
| Gestational hypertension | 1/135 (0.7%) | |
| Renal and urinary disorders | ||
| Renal pain | 1/135 (0.7%) | |
| Renal cyst haemorrhage | 2/135 (1.5%) | |
| Renal cyst ruptured | 1/135 (0.7%) | |
Other (Not Including Serious) Adverse Events |
||
| Tolvaptan | ||
| Affected / at Risk (%) | # Events | |
| Total | 134/135 (99.3%) | |
| Blood and lymphatic system disorders | ||
| Iron deficiency anaemia | 3/135 (2.2%) | |
| Cardiac disorders | ||
| Palpitations | 3/135 (2.2%) | |
| Tachycardia | 3/135 (2.2%) | |
| Ventricular extrasystoles | 3/135 (2.2%) | |
| Congenital, familial and genetic disorders | ||
| Congenital cystic kidney disease | 3/135 (2.2%) | |
| Ear and labyrinth disorders | ||
| Vertigo | 3/135 (2.2%) | |
| Eye disorders | ||
| Conjunctival haemorrhage | 5/135 (3.7%) | |
| Dry eye | 3/135 (2.2%) | |
| Glaucoma | 3/135 (2.2%) | |
| Gastrointestinal disorders | ||
| Abdominal discomfort | 8/135 (5.9%) | |
| Abdominal pain | 6/135 (4.4%) | |
| Abdominal pain lower | 3/135 (2.2%) | |
| Abdominal pain upper | 5/135 (3.7%) | |
| Constipation | 7/135 (5.2%) | |
| Dental caries | 10/135 (7.4%) | |
| Diarrhoea | 21/135 (15.6%) | |
| Enterocolitis | 3/135 (2.2%) | |
| Gastritis | 4/135 (3%) | |
| Gastrooesophageal reflux disease | 5/135 (3.7%) | |
| Nausea | 11/135 (8.1%) | |
| Stomatitis | 6/135 (4.4%) | |
| Vomiting | 10/135 (7.4%) | |
| General disorders | ||
| Chest pain | 5/135 (3.7%) | |
| Malaise | 5/135 (3.7%) | |
| Oedema peripheral | 8/135 (5.9%) | |
| Pyrexia | 8/135 (5.9%) | |
| Thirst | 104/135 (77%) | |
| Hepatobiliary disorders | ||
| Hepatic function abnormal | 14/135 (10.4%) | |
| Hepatic steatosis | 3/135 (2.2%) | |
| Immune system disorders | ||
| Seasonal allergy | 5/135 (3.7%) | |
| Infections and infestations | ||
| Conjunctivitis | 3/135 (2.2%) | |
| Gastroenteritis | 13/135 (9.6%) | |
| Hordeolum | 4/135 (3%) | |
| Influenza | 20/135 (14.8%) | |
| Nasopharyngitis | 94/135 (69.6%) | |
| Pharyngitis | 4/135 (3%) | |
| Sinusitis | 3/135 (2.2%) | |
| Viral infection | 3/135 (2.2%) | |
| Renal cyst infection | 4/135 (3%) | |
| Oral herpes | 5/135 (3.7%) | |
| Injury, poisoning and procedural complications | ||
| Arthropod sting | 3/135 (2.2%) | |
| Ligament sprain | 4/135 (3%) | |
| Contusion | 5/135 (3.7%) | |
| Investigations | ||
| Blood creatine phosphokinase increased | 6/135 (4.4%) | |
| Blood creatinine increased | 12/135 (8.9%) | |
| Blood pressure increased | 4/135 (3%) | |
| Gamma-glutamyltransferase increased | 3/135 (2.2%) | |
| Weight decreased | 8/135 (5.9%) | |
| Weight increased | 5/135 (3.7%) | |
| Hepatic enzyme increased | 4/135 (3%) | |
| Metabolism and nutrition disorders | ||
| Dehydration | 3/135 (2.2%) | |
| Diabetes mellitus | 3/135 (2.2%) | |
| Hyperuricaemia | 29/135 (21.5%) | |
| Dyslipidaemia | 4/135 (3%) | |
| Decreased appetite | 6/135 (4.4%) | |
| Hyperlipidaemia | 4/135 (3%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 3/135 (2.2%) | |
| Back pain | 30/135 (22.2%) | |
| Flank pain | 5/135 (3.7%) | |
| Muscle spasms | 6/135 (4.4%) | |
| Musculoskeletal pain | 3/135 (2.2%) | |
| Neck pain | 4/135 (3%) | |
| Spinal osteoarthritis | 3/135 (2.2%) | |
| Intervertebral disc protrusion | 4/135 (3%) | |
| Musculoskeletal stiffness | 3/135 (2.2%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Skin papilloma | 3/135 (2.2%) | |
| Nervous system disorders | ||
| Dizziness | 10/135 (7.4%) | |
| Dizziness postural | 5/135 (3.7%) | |
| Dysgeusia | 3/135 (2.2%) | |
| Headache | 26/135 (19.3%) | |
| Hypoaesthesia | 3/135 (2.2%) | |
| Intracranial aneurysm | 4/135 (3%) | |
| Psychiatric disorders | ||
| Depression | 4/135 (3%) | |
| Insomnia | 8/135 (5.9%) | |
| Renal and urinary disorders | ||
| Dysuria | 4/135 (3%) | |
| Haematuria | 6/135 (4.4%) | |
| Nocturia | 6/135 (4.4%) | |
| Pollakiuria | 77/135 (57%) | |
| Polyuria | 52/135 (38.5%) | |
| Renal cyst haemorrhage | 5/135 (3.7%) | |
| Renal impairment | 10/135 (7.4%) | |
| Reproductive system and breast disorders | ||
| Dysmenorrhoea | 4/135 (3%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Asthma | 3/135 (2.2%) | |
| Cough | 4/135 (3%) | |
| Upper respiratory tract inflammation | 21/135 (15.6%) | |
| Oropharyngeal pain | 3/135 (2.2%) | |
| Skin and subcutaneous tissue disorders | ||
| Dry skin | 4/135 (3%) | |
| Eczema | 7/135 (5.2%) | |
| Pruritus | 4/135 (3%) | |
| Rash | 6/135 (4.4%) | |
| Urticaria | 5/135 (3.7%) | |
| Vascular disorders | ||
| Hypertension | 20/135 (14.8%) | |
| Hypotension | 5/135 (3.7%) | |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Director of Clinical Trials |
|---|---|
| Organization | Otsuka Pharmaceutical Co., LTD. |
| Phone | +81-3-6361-7366 |
Responsible Party:
Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01280721
Other Study ID Numbers:
- 156-10-003
- JapicCTI-101362
First Posted:
Jan 21, 2011
Last Update Posted:
Jan 17, 2019
Last Verified:
Aug 1, 2018