A Study of AZD4901 in Females With Polycystic Ovary Syndrome
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01872078
Collaborator
(none)
67
7
4
13
9.6
0.7
Study Details
Study Description
Brief Summary
To assess the effects of AZD4901 when given in multiple doses to females with Polycystic Ovary Syndrome
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
67 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
A Randomised, Double-blind, Placebo-controlled Phase IIa Study to Assess the Pharmacodynamics, Safety, and Pharmacokinetics of AZD4901 When Given in Multiple Doses to Females With Polycystic Ovary Syndrome
Study Start Date
:
Jun 1, 2013
Actual Primary Completion Date
:
Jul 1, 2014
Actual Study Completion Date
:
Jul 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AZD4901 20 mg once a day AZD4901 20 mg once a day |
Drug: AZD4901 (oral)
Patients randomized to 1 of 4 treatment groups: AZD4901 20 mg once a day, AZD4901 20 mg twice a day, AZD4901 40 mg twice a day or placebo
|
| Experimental: AZD4901 20mg twice a day AZD4901 20mg twice a day |
Drug: AZD4901 (oral)
Patients randomized to 1 of 4 treatment groups: AZD4901 20 mg once a day, AZD4901 20 mg twice a day, AZD4901 40 mg twice a day or placebo
|
| Experimental: AZD4901 40 mg twice a day AZD4901 40 mg twice a day |
Drug: AZD4901 (oral)
Patients randomized to 1 of 4 treatment groups: AZD4901 20 mg once a day, AZD4901 20 mg twice a day, AZD4901 40 mg twice a day or placebo
|
| Experimental: Placebo to match AZD4901
|
Drug: Placebo to match AZD4901
Patients randomized to 1 of 4 treatment groups: AZD4901 20 mg once a day, AZD4901 20 mg twice a day, AZD4901 40 mg twice a day or placebo
|
Outcome Measures
Primary Outcome Measures
- Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7 [Day 7]
Change-from-baseline of luteinising hormone area under the concentration-time curve from time zero to 8 hours postdose [AUC(0-8)] at Day 7
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 45 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
Female patients between the ages of 18 to 45 years (inclusive). Suitable veins for cannulation or repeated venipuncture. Body mass index (BMI) between 18 and 40 kg/m2 (inclusive). A diagnosis of polycystic ovary disease. Amenorrhea or oligomenorrhea (defined as ≤ 6 menses per year). Negative serum pregnancy test at screening. Negative urine pregnancy test before randomisation. Not be breast-feeding. Not have been pregnant within the 6 months prior to screening.
Exclusion Criteria:
Perimenopausal or reached natural menopause, defined as FSH > 10 IU/L. Menstruated within the month prior to the baseline visit. Hysterectomy or bilateral oophorectomy or both. Clinically relevant disease and abnormalities (past or present), and in particular causes of abnormal vaginal bleeding.
Withdrawals from oral contraceptives if their LH levels are below 3 IU/L when retested within 7 ± 1 days of the baseline visit.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Miami Research Associates | Miami | Florida | United States | |
| 2 | Research Site | Orlando | Florida | United States | |
| 3 | Research Site | Springfield | Missouri | United States | |
| 4 | Research Site | Berlin | Germany | ||
| 5 | Research Site | Belfast | United Kingdom | ||
| 6 | Research Site | Edinburgh | United Kingdom | ||
| 7 | Research Site | London | United Kingdom |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Jyothis George, MD, University of Oxford
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01872078
Other Study ID Numbers:
- D5320C00001
First Posted:
Jun 7, 2013
Last Update Posted:
Oct 12, 2015
Last Verified:
Sep 1, 2015
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 67 patients were recruited to the study, of which 65 received doses of AZD4901 between 20 mg qd and 40 mg bid or placebo. Two patients were excluded due to poor venous access |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | 20 mg AZD4901 Once Daily | 20 mg AZD4901 Twice Daily | 40 mg AZD4901 Twice Daily |
|---|---|---|---|---|
| Arm/Group Description | Two matching placebo tablets for both the morning and evening doses | One 20-mg AZD4901 tablet and 1 placebo tablet for the morning dose and 2 placebo tablets for the evening dose | One 20-mg AZD4901 tablet and 1 placebo tablet for both the morning and evening doses | Two 20-mg AZD4901 tablets for both the morning and evening doses |
| Period Title: Overall Study | ||||
| STARTED | 16 | 15 | 17 | 17 |
| COMPLETED | 16 | 15 | 14 | 15 |
| NOT COMPLETED | 0 | 0 | 3 | 2 |
Baseline Characteristics
| Arm/Group Title | Placebo | 20 mg AZD4901 Once Daily | 20 mg AZD4901 Twice Daily | 40 mg AZD4901 Twice Daily | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Two matching placebo tablets for both the morning and evening doses | One 20-mg AZD4901 tablet and 1 placebo tablet for the morning dose and 2 placebo tablets for the evening dose | One 20-mg AZD4901 tablet and 1 placebo tablet for both the morning and evening doses | Two 20-mg AZD4901 tablets for both the morning and evening doses | Total of all reporting groups |
| Overall Participants | 16 | 15 | 17 | 17 | 65 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
27
(3)
|
29
(6)
|
27
(6)
|
28
(6)
|
28
(6)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
16
100%
|
15
100%
|
17
100%
|
17
100%
|
65
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Lutenising Hormone (LH) AUC(0-8) Ratio to Baseline at Day 7 |
|---|---|
| Description | Change-from-baseline of luteinising hormone area under the concentration-time curve from time zero to 8 hours postdose [AUC(0-8)] at Day 7 |
| Time Frame | Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | 20 mg AZD4901 qd | 20 mg AZD4901 Bid | 40 mg AZD4901 Bid |
|---|---|---|---|---|
| Arm/Group Description | Two matching placebo tablets for both the morning and evening doses | 20 mg AZD4901 once daily administered orally | 20 mg AZD4901 twice daily administered orally | 40 mg AZD4901 twice daily administered orally |
| Measure Participants | 13 | 13 | 14 | 15 |
| Geometric Mean (95% Confidence Interval) [Ratio] |
1.118
|
0.9729
|
0.8804
|
0.5364
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 20 mg AZD4901 qd |
|---|---|---|
| Comments | The null hypothesis is that the ratio of Active to Control in LH AUC(0-8) ratio to baseline at day 7= 100% | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio (%) |
| Estimated Value | 87.04 | |
| Confidence Interval |
(2-Sided) 95% 58.52 to 129.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 20 mg AZD4901 Bid |
|---|---|---|
| Comments | The null hypothesis is that the ratio of Active to Control in LH AUC(0-8) ratio to baseline at day 7= 100% | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio (%) |
| Estimated Value | 78.76 | |
| Confidence Interval |
(2-Sided) 95% 53.41 to 116.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, 40 mg AZD4901 Bid |
|---|---|---|
| Comments | The null hypothesis is that the ratio of Active to Control in LH AUC(0-8) ratio to baseline at day 7= 100% | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio (%) |
| Estimated Value | 47.99 | |
| Confidence Interval |
(2-Sided) 95% 32.73 to 70.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | 20 mg AZD4901 Once Daily | 20 mg AZD4901 Twice Daily | 40 mg AZD4901 Twice Daily | Placebo | ||||
| Arm/Group Description | One 20-mg AZD4901 tablet and 1 placebo tablet for the morning dose and 2 placebo tablets for the evening dose | One 20-mg AZD4901 tablet and 1 placebo tablet for both the morning and evening doses | Two 20-mg AZD4901 tablets for both the morning and evening doses | Two matching placebo tablets for both the morning and evening doses | ||||
All Cause Mortality |
||||||||
| 20 mg AZD4901 Once Daily | 20 mg AZD4901 Twice Daily | 40 mg AZD4901 Twice Daily | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| 20 mg AZD4901 Once Daily | 20 mg AZD4901 Twice Daily | 40 mg AZD4901 Twice Daily | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Infections and infestations | ||||||||
| Appendicitis | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| 20 mg AZD4901 Once Daily | 20 mg AZD4901 Twice Daily | 40 mg AZD4901 Twice Daily | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/15 (40%) | 13/17 (76.5%) | 5/17 (29.4%) | 6/16 (37.5%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear pain | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Eye disorders | ||||||||
| Conjunctivitis | 1/15 (6.7%) | 0/17 (0%) | 0/17 (0%) | 0/16 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Abdominal pain | 1/15 (6.7%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Abdominal pain lower | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Abdominal pain upper | 1/15 (6.7%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Nausea | 1/15 (6.7%) | 0/17 (0%) | 0/17 (0%) | 1/16 (6.3%) | ||||
| Constipation | 1/15 (6.7%) | 0/17 (0%) | 0/17 (0%) | 0/16 (0%) | ||||
| Diarrhoea | 0/15 (0%) | 0/17 (0%) | 1/17 (5.9%) | 0/16 (0%) | ||||
| General disorders | ||||||||
| Nodule | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Influenza Like Illness | 0/15 (0%) | 0/17 (0%) | 1/17 (5.9%) | 1/16 (6.3%) | ||||
| Pyrexia | 0/15 (0%) | 0/17 (0%) | 1/17 (5.9%) | 0/16 (0%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 2/15 (13.3%) | 1/17 (5.9%) | 1/17 (5.9%) | 1/16 (6.3%) | ||||
| Upper respiratory tract infection | 1/15 (6.7%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Appendicitis | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Vulvovaginal Mycotic Infection | 1/15 (6.7%) | 0/17 (0%) | 0/17 (0%) | 0/16 (0%) | ||||
| Gastrointestinal Infection | 0/15 (0%) | 0/17 (0%) | 0/17 (0%) | 1/16 (6.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Procedural dizziness | 0/0 (NaN) | 1/1 (100%) | 0/0 (NaN) | 0/0 (NaN) | ||||
| Tooth fracture | 0/0 (NaN) | 1/1 (100%) | 0/0 (NaN) | 0/0 (NaN) | ||||
| Muscle Strain | 1/15 (6.7%) | 0/17 (0%) | 0/17 (0%) | 0/16 (0%) | ||||
| Investigations | ||||||||
| Hepatic Enzyme Increased | 2/15 (13.3%) | 0/17 (0%) | 0/17 (0%) | 0/16 (0%) | ||||
| Alanine Aminotransferase Increased | 0/15 (0%) | 0/17 (0%) | 1/17 (5.9%) | 0/16 (0%) | ||||
| Aspartate Aminotransferase Increased | 0/15 (0%) | 0/17 (0%) | 1/17 (5.9%) | 0/16 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscle Spasms | 1/15 (6.7%) | 0/17 (0%) | 1/17 (5.9%) | 0/16 (0%) | ||||
| Nervous system disorders | ||||||||
| Headache | 2/15 (13.3%) | 3/17 (17.6%) | 4/17 (23.5%) | 5/16 (31.3%) | ||||
| Migraine | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Presyncope | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Syncope | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Dizziness | 1/15 (6.7%) | 0/17 (0%) | 1/17 (5.9%) | 1/16 (6.3%) | ||||
| Renal and urinary disorders | ||||||||
| Nephrolithiasis | 0/15 (0%) | 0/17 (0%) | 1/17 (5.9%) | 0/16 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Vaginal haemorrhage | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 1/16 (6.3%) | ||||
| Pelvic Pain | 1/15 (6.7%) | 0/17 (0%) | 0/17 (0%) | 0/16 (0%) | ||||
| Vaginal Discharge | 0/15 (0%) | 0/17 (0%) | 0/17 (0%) | 1/16 (6.3%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Rhinitis allergic | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Sleep apnoea syndrome | 0/15 (0%) | 1/17 (5.9%) | 0/17 (0%) | 0/16 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 0/15 (0%) | 1/17 (5.9%) | 1/17 (5.9%) | 0/16 (0%) | ||||
| Rash | 0/15 (0%) | 2/17 (11.8%) | 0/17 (0%) | 0/16 (0%) | ||||
| Vascular disorders | ||||||||
| Hot Flush | 0/15 (0%) | 0/17 (0%) | 1/17 (5.9%) | 0/16 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AstraZeneca will manage the publication of the results of the Clinical Trial in partnership with the authors. AstraZeneca recognises that Institutions/Investigators may wish to make publications regarding Clinical Trial results. The Institution/Investigator agrees to collaborate in good faith with AstraZeneca. Prior to any such publication, the Institution/Investigator shall provide AstraZeneca with preliminary data and drafts of proposed publications.
Results Point of Contact
| Name/Title | Martin L. Scott, MD/PhD |
|---|---|
| Organization | AstraZeneca Pharmaceuticals LP |
| Phone | 781-472-5130 |
| martin.scott@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01872078
Other Study ID Numbers:
- D5320C00001
First Posted:
Jun 7, 2013
Last Update Posted:
Oct 12, 2015
Last Verified:
Sep 1, 2015