Trial Outcomes & Findings for Study to Evaluate the Effect of Celecoxib on the Efficacy and Safety of Amlodipine in Subjects With Hypertension Requiring Antihypertensive Therapy (NCT NCT02172040)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

152 participants

Primary outcome timeframe

Baseline and 2 weeks

Results posted on

2018-10-10

Participant Flow

Participants underwent assessments to determine eligibility at the Initial Screening Visit (Day -7 to -2; 458 participants), Final Screening Visit (Day -1; 228 participants), and the morning prior to randomization (Study Day 0; 227 participants). A total of 306 participants were screen failures and the remaining 152 were randomized.

Participant milestones

Participant milestones
Measure	Amlodipine+Celecoxib Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Overall Study STARTED	49	45	31	27
Overall Study COMPLETED	49	42	29	26
Overall Study NOT COMPLETED	0	3	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Amlodipine+Placebo Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Overall Study Adverse Event	2	0	0
Overall Study Protocol Violation	1	0	0
Overall Study Withdrawal by Subject	0	1	0
Overall Study Not available for Day 13 & 14 visits	0	1	0
Overall Study Family emergency abroad	0	0	1

Baseline Characteristics

Study to Evaluate the Effect of Celecoxib on the Efficacy and Safety of Amlodipine in Subjects With Hypertension Requiring Antihypertensive Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=31 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=27 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Total n=152 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 8.0 • n=5 Participants	57.3 years STANDARD_DEVIATION 9.4 • n=7 Participants	54.9 years STANDARD_DEVIATION 8.2 • n=5 Participants	52.5 years STANDARD_DEVIATION 9.1 • n=4 Participants	56.1 years STANDARD_DEVIATION 8.8 • n=21 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	19 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	56 Participants n=21 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	26 Participants n=7 Participants	21 Participants n=5 Participants	17 Participants n=4 Participants	96 Participants n=21 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
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	43 Participants n=7 Participants	29 Participants n=5 Participants	26 Participants n=4 Participants	144 Participants n=21 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
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
Region of Enrollment United Kingdom	49 Participants n=5 Participants	45 Participants n=7 Participants	31 Participants n=5 Participants	27 Participants n=4 Participants	152 Participants n=21 Participants
Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday)	148.7 mmHg STANDARD_DEVIATION 7.4 • n=5 Participants	147.6 mmHg STANDARD_DEVIATION 8.7 • n=7 Participants	150.8 mmHg STANDARD_DEVIATION 8.9 • n=5 Participants	147.3 mmHg STANDARD_DEVIATION 8.6 • n=4 Participants	148.5 mmHg STANDARD_DEVIATION 8.4 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline and 2 weeks

Population: Intent-to-treat (ITT): All randomized participants who received at least 1 dose of study drug and had at least a valid baseline ambulatory blood pressure monitor measurement (ABPM) and either: a) a valid Day 13-14 ABPM, where participant completed treatment or b) a valid Day 6-7 or Day 0-1 ABPM, where participant was withdrawn early.

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=30 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=26 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Primary Endpoint	-10.6 mmHg Standard Deviation 9.2	-8.83 mmHg Standard Deviation 8.13	-0.5 mmHg Standard Deviation 8.8	-2.11 mmHg Standard Deviation 8.2

PRIMARY outcome

Timeframe: 1 month

Population: Safety population: all randomized participants who received at least one dose of study drug.

Including any untoward medical occurrence in a participant administered study drug, which do not necessarily have a causal relationship with the study drug \[i.e., any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not related to the study drug\].

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=31 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=27 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Frequency of Adverse Events (Number of Participants Affected/Number of Participants at Risk)	27 Participants	28 Participants	14 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline and 2 weeks

Population: ITT population as described for primary outcome

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=30 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=26 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Change in Average 24-hour Ambulatory Systolic Blood Pressure (SBP24h)	-10.3 mmHg Standard Deviation 8.9	-8.02 mmHg Standard Deviation 7.6	-0.5 mmHg Standard Deviation 7.8	-1.19 mmHg Standard Deviation 5.87

SECONDARY outcome

Timeframe: Baseline and 2 weeks

Population: ITT Population as described for primary outcome

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=30 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=26 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Systolic Blood Pressure (SBPnight)	-10.5 mmHg Standard Deviation 10.6	-6.35 mmHg Standard Deviation 11.35	-1.7 mmHg Standard Deviation 12.3	-1.42 mmHg Standard Deviation 9.15

SECONDARY outcome

Timeframe: Baseline and 2 weeks

Population: ITT Population as described for primary outcome

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=30 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=26 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Change in Average 24-hour Ambulatory Diastolic Blood Pressure (DBP24h)	-7.1 mmHg Standard Deviation 5.6	-4.8 mmHg Standard Deviation 4.83	-0.5 mmHg Standard Deviation 4.6	0.22 mmHg Standard Deviation 4.28

SECONDARY outcome

Timeframe: Baseline and 2 weeks

Population: ITT Population as described for primary outcome

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=30 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=26 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Diastolic Blood Pressure (DBPday)	-7.5 mmHg Standard Deviation 6.4	-5.53 mmHg Standard Deviation 5.06	-1.5 mmHg Standard Deviation 5.6	-0.32 mmHg Standard Deviation 5.39

SECONDARY outcome

Timeframe: Baseline and 2 weeks

Population: ITT Population as defined for primary outcome

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=30 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=26 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Change in Average Night-time (01:00 to 06:00) Ambulatory Diastolic Blood Pressure (DBPnight)	-7.0 mmHg Standard Deviation 8.6	-3.23 mmHg Standard Deviation 7.79	0.3 mmHg Standard Deviation 7.1	0.01 mmHg Standard Deviation 6.23

SECONDARY outcome

Timeframe: 24 hours post-dose on Day 14

Population: Pharmacokinetic (PK) population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No amlodipine PK statistical analyses were performed for the PK participants in the placebo+celecoxib and placebo+placebo arms.

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=24 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=20 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Non-transformed Amlodipine Plasma Concentration	15,800.83 pg/mL Standard Deviation 4,161.929	23,453 pg/mL Standard Deviation 5,746.337	—	—

SECONDARY outcome

Timeframe: 24 hours post-dose on Day 14

Population: PK population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No celecoxib PK statistical analyses were performed for the PK participants in the amlodipine+placebo and placebo+placebo arms.

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=24 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=15 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Non-transformed Celecoxib Plasma Concentration	139.708 ng/mL Standard Deviation 86.504	138.667 ng/mL Standard Deviation 118.811	—	—

SECONDARY outcome

Timeframe: 24 hours post-dose on Day 14

Population: PK population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No amlodipine PK statistical analyses were performed for the PK participants in the placebo+celecoxib and placebo+placebo arms.

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=24 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=20 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Log-transformed Amlodipine Plasma Concentration	9.634 log(pg/mL) Standard Deviation 0.268	10.025 log(pg/mL) Standard Deviation 0.310	—	—

SECONDARY outcome

Timeframe: 24 hours post-dose on Day 14

Population: PK population: subset of overall trial population, consisting of participants at Investigational sites capable of obtaining PK blood samples in a protected light environment. No celecoxib PK statistical analyses were performed for the PK participants in the amlodipine+placebo and placebo+placebo arms.

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=24 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=15 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Log-transformed Celecoxib Plasma Concentration	4.785 log(ng/mL) Standard Deviation 0.564	4.636 log(ng/mL) Standard Deviation 0.781	—	—

SECONDARY outcome

Timeframe: Baseline and 2 weeks

Population: ITT Population as described for primary outcome

Outcome measures

Outcome measures
Measure	Amlodipine+Celecoxib n=49 Participants Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 Participants Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=30 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=26 Participants Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Mean Change in Average Daytime (9:00 to 21:00) Ambulatory Systolic Blood Pressure (SBPday) - Secondary Endpoint	-10.6 mmHg Standard Deviation 9.2	-8.83 mmHg Standard Deviation 8.13	-0.5 mmHg Standard Deviation 8.8	-2.11 mmHg Standard Deviation 8.2

Adverse Events

Amlodipine+Celecoxib

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Amlodipine+Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo+Celecoxib

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo+Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Amlodipine+Celecoxib n=49 participants at risk Over-encapsulated 10 mg amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks	Amlodipine+Placebo n=45 participants at risk Over-encapsulated 10 mg amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Over-encapsulated 10 mg amlodipine besylate tablet: Over-encapsulated 10 mg amlodipine besylate tablet once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks	Placebo+Celecoxib n=31 participants at risk Matched placebo tablet for over-encapsulated amlodipine besylate tablet + over-encapsulated 200 mg celecoxib capsule once a day for two weeks Over-encapsulated 200 mg celecoxib capsule: Over-encapsulated 200 mg celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks	Placebo+Placebo n=27 participants at risk Matched placebo tablet for over-encapsulated amlodipine besylate tablet + matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo capsule for over-encapsulated celecoxib capsule: Matched placebo capsule for over-encapsulated celecoxib capsule once a day for two weeks Matched placebo tablet for over-encapsulated amlodipine besylate tablet: Matched placebo tablet for over-encapsulated amlodipine besylate tablet once a day for two weeks
Gastrointestinal disorders Diarrhoea	4.1% 2/49 • Number of events 2 • 1 month	8.9% 4/45 • Number of events 4 • 1 month	0.00% 0/31 • 1 month	0.00% 0/27 • 1 month
General disorders Oedema peripheral	8.2% 4/49 • Number of events 4 • 1 month	15.6% 7/45 • Number of events 8 • 1 month	0.00% 0/31 • 1 month	0.00% 0/27 • 1 month
Infections and infestations Nasopharyngitis	10.2% 5/49 • Number of events 5 • 1 month	0.00% 0/45 • 1 month	6.5% 2/31 • Number of events 2 • 1 month	0.00% 0/27 • 1 month
Infections and infestations Upper respiratory tract infection	0.00% 0/49 • 1 month	4.4% 2/45 • Number of events 3 • 1 month	6.5% 2/31 • Number of events 2 • 1 month	3.7% 1/27 • Number of events 1 • 1 month
Metabolism and nutrition disorders Gout	0.00% 0/49 • 1 month	0.00% 0/45 • 1 month	0.00% 0/31 • 1 month	7.4% 2/27 • Number of events 2 • 1 month
Musculoskeletal and connective tissue disorders Joint swelling	10.2% 5/49 • Number of events 5 • 1 month	6.7% 3/45 • Number of events 4 • 1 month	0.00% 0/31 • 1 month	0.00% 0/27 • 1 month
Nervous system disorders Headache	8.2% 4/49 • Number of events 5 • 1 month	13.3% 6/45 • Number of events 10 • 1 month	6.5% 2/31 • Number of events 3 • 1 month	7.4% 2/27 • Number of events 2 • 1 month
Vascular disorders Orthostatic hypotension	0.00% 0/49 • 1 month	4.4% 2/45 • Number of events 3 • 1 month	0.00% 0/31 • 1 month	7.4% 2/27 • Number of events 2 • 1 month

Additional Information

J. Paul Waymack, M.D., Chief Medical Officer

Kitov Pharmaceuticals, Ltd.

Phone: (202) 965-2215

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60